US2510731A - Method of making alkyldihydrothebainones - Google Patents
Method of making alkyldihydrothebainones Download PDFInfo
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- US2510731A US2510731A US667108A US66710846A US2510731A US 2510731 A US2510731 A US 2510731A US 667108 A US667108 A US 667108A US 66710846 A US66710846 A US 66710846A US 2510731 A US2510731 A US 2510731A
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- US
- United States
- Prior art keywords
- methyldihydrothebainone
- making
- methyl magnesium
- dihydrocodeinone
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 238000004519 manufacturing process Methods 0.000 title claims description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 45
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 18
- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 claims description 15
- 229960000240 hydrocodone Drugs 0.000 claims description 15
- -1 METHYL MAGNESIUM HALIDE Chemical class 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 claims description 8
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 claims description 7
- 239000000243 solution Substances 0.000 description 13
- 239000007818 Grignard reagent Substances 0.000 description 12
- 150000004795 grignard reagents Chemical class 0.000 description 8
- 239000003849 aromatic solvent Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229930013930 alkaloid Natural products 0.000 description 3
- 150000003797 alkaloid derivatives Chemical class 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 229910001623 magnesium bromide Inorganic materials 0.000 description 3
- 229910001641 magnesium iodide Inorganic materials 0.000 description 3
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- FQXXSQDCDRQNQE-UHFFFAOYSA-N markiertes Thebain Natural products COC1=CC=C2C(N(CC3)C)CC4=CC=C(OC)C5=C4C23C1O5 FQXXSQDCDRQNQE-UHFFFAOYSA-N 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229930003945 thebaine Natural products 0.000 description 2
- FQXXSQDCDRQNQE-VMDGZTHMSA-N thebaine Chemical compound C([C@@H](N(CC1)C)C2=CC=C3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 FQXXSQDCDRQNQE-VMDGZTHMSA-N 0.000 description 2
- XJZOLKDBHJPTAT-ATNYCFDYSA-N (4r,4ar,7ar,12bs)-7,9-dimethoxy-3-methyl-2,4,4a,5,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline Chemical compound C([C@@H](N(CC1)C)[C@@H]2CC=C3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 XJZOLKDBHJPTAT-ATNYCFDYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000003842 bromide salts Chemical class 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- CDGFTOARGCEWKI-IYOUNJFTSA-N dihydrothebainone Chemical compound C([C@H]12)CC(=O)C[C@@]11CCN(C)[C@@H]2CC2=CC=C(OC)C(O)=C21 CDGFTOARGCEWKI-IYOUNJFTSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000005649 metathesis reaction Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- NPZXCTIHHUUEEJ-CMKMFDCUSA-N metopon Chemical compound O([C@@]1(C)C(=O)CC[C@@H]23)C4=C5[C@@]13CCN(C)[C@@H]2CC5=CC=C4O NPZXCTIHHUUEEJ-CMKMFDCUSA-N 0.000 description 1
- 229950006080 metopon Drugs 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 239000004081 narcotic agent Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
- C07D221/28—Morphinans
Definitions
- This invention relates to the. manufacture. of narcotics and more articularly to. methodsior them-operation of intermediates for. the manu-. iacture of methyldihydromorphinone.
- the invention accordingly comprises the steps and sequence of steps, and features ofsynthesis, analysis, or metathesis, which will; be. exemplifled. in the processes hereinafter described, and the. scope of the application of which. wilLbe-indicated in the following. claims.
- methyldihydroinon. phinone In the manufacture of. methyldihydroinon. phinone. one of the, intermediates customarily, utilized; is. methyldihydrothebainone. This. in: termediate may be. prepared from thebaine by hydrogenation to dihydrothebaine, followed by reaction with a. Grignard reagent. to formin'ethe yldihydrothehainone It' has been found, hows ever, that on hydrogenation of thebaine, relatively small. quantities of dihydrothebaineiv are. obtained. together with larger quantities ofv dihydrothebainone.
- Dihydrotheoainone has. been of'limited utility because to convert. ittothe desired methyldihy-- drothebainone ithasbeen necessary-toifirstform dihydrocodeinone, then the acetate or the enol' forinof dihydrocodeinone, and then to form the desired methyl derivative, methyldihydrothebainone.-
- Example I Two molesof methyl magnesium iodide solution. (1310. cc. of. 1.53 N), was distilled in a 5 liter,
- the'complex was decomposed by adding to the flask excess dilute hydrochloric acid (about 350 1 cc. concentrated hydrochloric acid diluted to 2 liters) and the benzene layer was separated and washed with dilute hydrochloric acid'whichwasadded-to the main aqueous phase.
- the aqueous phase- was stirred with 1 liter of chloroform and ammonia-cal by adding a small excess of" 1 1.1 g, or"4:7-% of the theoreticalyield;
- Example II itizruetherv solution. of-206cc. ofmethyl mag l cur 580 cc. portions of chloroform and the" inedextracts were distilled to dryness.
- 270 cc. of dry benzene was added and the condenser was arranged for refluxing. After bringing to refluxing temperature, a warm solution of 40 grams of dihydrocodeinone in 700 cc. of dry benzene was added during 18 minutes. The solution was stirred and refluxed for one and one-half hours and then was refluxed without stirring for four and one half hours more.
- methyl magnesium halides may be substituted for the methyl magnesium iodide and methyl magnesium bromide respectively described.
- Example IV 72.5 grams of crude methyldihydrothebainone hydrochloride was dissolved in 300 cc. of hot water, decolorized with activated carbon and after filtering, 40 grams of sodium bromide was added. Methyldihydrothebainone hydrobromide crystallized rapidly. After cooling it was filtered off and washed with alcohol. The slightly moist hydrobromide weighed 71 grams.
- the hydrobromide of methyldihydrothebainone can be prepared by reacting the alkaloid with hydrobromic acid or it can be formed by treating the hydrochloride of the alkaloid with a bromide salt.
- the hydrobromide is of particular value. For example, it has more desirable solubility characteristics than the hydrochloride, and is accordingly of a special utility for purifying the alkaloid.
- homologs of methyldihydrothebainone may be prepared in an analogous manner by using an appropriate Grignard reagent.
- chloroform is not only an efiective solvent for this purpose, but it has certain advantages over the previously utilized solvents. For example, extraction with ether is hazardous and clumsy on account of the large volumes of solvent required. Extraction with benzene has a tendency to form stubborn emulsions. Chloroform as a solvent for this purpose is not subject to the foregoing disadvantages. Relatively small proportions of chloroform are effective to extract the methyldihydrothebainone efiiciently from its aqueous solution.
- methyldihydrothebainone which comprises adding dihydrocodeinone in an aromatic solvent to a methyl Grignard reagent selected from the group consisting of a methyl magnesium bromide and a methyl magnesium iodide in an aromatic solvent.
- methyldihydrothebainone which comprises adding dihydrocodeinone to a methyl Grignard reagent selected from the group consisting of a methyl magnesium bromide and a methyl magnesium iodide in benzene.
- methyldihydrothebainone which comprises adding dihydrocodeinone in benzene to a methyl Grignard reagent selected from the group consisting of a methyl magnesium bromide and a methyl magnesium iodide in benzene.
- methyldihydrothebainone which comprises removing the major portion of the solvent ether from an ethereal solution of a methyl Grignard reagent selected from the group consisting of a methyl magnesium bromide and a methyl magnesium iodide, adding an aromatic solvent to said Grignard reagent and then adding dihydrocodeinone.
- a methyl Grignard reagent selected from the group consisting of a methyl magnesium bromide and a methyl magnesium iodide
- methyldihydrothebainone which comprises adding a benzene solution of dihydrocodeinone to a benzene solution of a methyl magnesium halide selected from the group consisting of a methyl magnesium bromide and a methyl magnesium iodide, decomposing the complex formed by adding excess dilute hydrochloric acid, extracting the methyldihydrothebainone with chloroform, purifying the product by forming a hydroha-lide of the methyldihydrothebainone.
- Fieser and Fieser Organic Chemistry (D. C. 2'364'833 Wemard 1 10 Heath'& Co., 1944; Boston); p. 39 and p.803.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Patented June 6, 1950 METHQD or. MAKING ALKYLDIHYDRO-- EBAINQNES.
Frank C. Whitmore, State College, Pa., and August H. Homeyer. Webster-Groves, Md, assigncrs to Mellinc rod h micat Works. St. Louis, Mo. a corporation of Missouri No Drawing. Application May 3, 1946, Serial No. 66?,108
V 9 Claims. (01.
This invention. relates to the. manufacture. of narcotics and more articularly to. methodsior them-operation of intermediates for. the manu-. iacture of methyldihydromorphinone.
Among the objects of this inventionaare the provision or methods, for the. utilization. of byproducts in the manufacture of derivativesof the morphine, series; the provision of .methods for improving the yield of desired products in the manufacture of derivatives of; the morphine series; and theprovision of methods. for more easily preparing intermediates for themanufacture of: methyldihydromorphinona.. Other ob-.- jects willbe in part apparent and inpart pointed out. hereinafter.
The invention accordingly comprises the steps and sequence of steps, and features ofsynthesis, analysis, or metathesis, which will; be. exemplifled. in the processes hereinafter described, and the. scope of the application of which. wilLbe-indicated in the following. claims.
In the manufacture of. methyldihydroinon. phinone. one of the, intermediates customarily, utilized; is. methyldihydrothebainone. This. in: termediate may be. prepared from thebaine by hydrogenation to dihydrothebaine, followed by reaction with a. Grignard reagent. to formin'ethe yldihydrothehainone It' has been found, hows ever, that on hydrogenation of thebaine, relatively small. quantities of dihydrothebaineiv are. obtained. together with larger quantities ofv dihydrothebainone.
Dihydrotheoainone has. been of'limited utility because to convert. ittothe desired methyldihy-- drothebainone ithasbeen necessary-toifirstform dihydrocodeinone, then the acetate or the enol' forinof dihydrocodeinone, and then to form the desired methyl derivative, methyldihydrothebainone.-
In accordance with the-present invention, however, it has been found that dihydrocodeinonecan be directly converted to methyldihydrothebainone without the intermediate formation,
to methyl-dihydrothebainoneby formation, for" example, of the acetyl derivative of'thezenol form:
of dihydrocodcinone, followed by reaction of this product with a Grignard reagent, are materially shortened and improved.
The following examples illustrate the invention:
Example I Two molesof methyl magnesium iodide solution. (1310. cc. of. 1.53 N), was distilled in a 5 liter,
three-necked flask fitted with amercury sealed stirrer, dropping funnel and condenser, until no more other came over with the bath at about C. One liter of. dry benzene was added to the residue, stirred, and heated to boiling, while a solution of 290 g. of dihydrocodeinone in 2 liters of dry benzene was added during 10 minutes. Distillation was continued by heating until 800 cc. of distillate were collected. Then the condenser was set for refluxing which was continued for 3 six hours. A voluminous white solid formed during the addition of the dihydrocodeinone to th'e Grignard reagent. At the end of the reaction, the'complex was decomposed by adding to the flask excess dilute hydrochloric acid (about 350 1 cc. concentrated hydrochloric acid diluted to 2 liters) and the benzene layer was separated and washed with dilute hydrochloric acid'whichwasadded-to the main aqueous phase. The aqueous phase-was stirred with 1 liter of chloroform and ammonia-cal by adding a small excess of" 1 1.1 g, or"4:7-% of the theoreticalyield;
Example II itizruetherv solution. of-206cc. ofmethyl mag l cur 580 cc. portions of chloroform and the" inedextracts were distilled to dryness. The methyldihydrothebainone' nesium bromide containing 0.4 mole was concentrated by distillation in a water bath until no more ether would distill. 270 cc. of dry benzene was added and the condenser was arranged for refluxing. After bringing to refluxing temperature, a warm solution of 40 grams of dihydrocodeinone in 700 cc. of dry benzene was added during 18 minutes. The solution was stirred and refluxed for one and one-half hours and then was refluxed without stirring for four and one half hours more. A test for the presence of a Grignard reagent was negative. The reaction mixture was decomposed by addition of excess dilute hydrochloric acid and then the solution was made alkaline with ammonia, and a little sodium hydrosulfite, NazSzOi, was added. The benzene layer was separated and the Water layer was extracted three times with chloroform. The benzene and chloroform extracts were combined, dried, and concentrated by distillation, the last traces of solvent being removed under reduced pressure. The residue, weighing 32.5 grams, was dissolved in 60 cc. of anhydrous alcohol and the solution was saturated with hydrogen chloride. A precipitate formed immediately and after storing in a refrigerator overnight, it was filtered off and washed with alcohol. The dry methyldihydrothebainone hydrochloride weighed 15.5 grams.
In the foregoing examples other methyl magnesium halides may be substituted for the methyl magnesium iodide and methyl magnesium bromide respectively described.
ExampZe III 12 grams of impure methyldihydrothebainone was suspended in 100 cc. of Water and dissolved by adding hydrobromic acid until all the solid was in solution and the solution was acid to Congo. The solution was decolorized with activated carbon and allowed to crystallize. The crystals of methyldihydrothebainone hydrobromide after drying weighed 12.6 grams.
Example IV 72.5 grams of crude methyldihydrothebainone hydrochloride was dissolved in 300 cc. of hot water, decolorized with activated carbon and after filtering, 40 grams of sodium bromide was added. Methyldihydrothebainone hydrobromide crystallized rapidly. After cooling it was filtered off and washed with alcohol. The slightly moist hydrobromide weighed 71 grams.
As shown in these examples the hydrobromide of methyldihydrothebainone can be prepared by reacting the alkaloid with hydrobromic acid or it can be formed by treating the hydrochloride of the alkaloid with a bromide salt. The hydrobromide is of particular value. For example, it has more desirable solubility characteristics than the hydrochloride, and is accordingly of a special utility for purifying the alkaloid.
It will be understood, of course, that homologs of methyldihydrothebainone may be prepared in an analogous manner by using an appropriate Grignard reagent.
The extraction of the crude methyldihydrothebainone is advantageously carried out by the use of chloroform as indicated in the foregoing examples. chloroform is not only an efiective solvent for this purpose, but it has certain advantages over the previously utilized solvents. For example, extraction with ether is hazardous and clumsy on account of the large volumes of solvent required. Extraction with benzene has a tendency to form stubborn emulsions. Chloroform as a solvent for this purpose is not subject to the foregoing disadvantages. Relatively small proportions of chloroform are effective to extract the methyldihydrothebainone efiiciently from its aqueous solution.
In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.
As many changes could be made in the above processes without departing from the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.
We claim:
1. The method of making an alkyldihydrothebainone which comprises adding dihydrocodeinone to a Grignard reagent selected from the group consisting of an alkyl magnesium bromide and an alkyl magnesium iodide in an aromatic solvent.
2. The method of making methyldihydrothebainone which comprises adding dihydrocodeinone in an aromatic solvent to a methyl Grignard reagent selected from the group consisting of a methyl magnesium bromide and a methyl magnesium iodide in an aromatic solvent.
3. The method of making methyldihydrothebainone which comprises adding dihydrocodeinone to a methyl Grignard reagent selected from the group consisting of a methyl magnesium bromide and a methyl magnesium iodide in benzene.
4. The method of making methyldihydrothebainone which comprises adding dihydrocodeinone in benzene to a methyl Grignard reagent selected from the group consisting of a methyl magnesium bromide and a methyl magnesium iodide in benzene.
5. The method of making methyldihydrothebainone which comprises removing the major portion of the solvent ether from an ethereal solution of a methyl Grignard reagent selected from the group consisting of a methyl magnesium bromide and a methyl magnesium iodide, adding an aromatic solvent to said Grignard reagent and then adding dihydrocodeinone.
6. The method of making methyldihydrothebainone which comprises adding a benzene solution of dihydrocodeinone to a benzene solution of a methyl magnesium halide selected from the group consisting of a methyl magnesium bromide and a methyl magnesium iodide, decomposing the complex formed by adding excess dilute hydrochloric acid, extracting the methyldihydrothebainone with chloroform, purifying the product by forming a hydroha-lide of the methyldihydrothebainone.
7. The method of making an alkyldihydrothebainone which comprises reacting dihydrocodeinone with a Grignard reagent selected from the group consisting of an alkyl magnesium bromide and an alkyl magnesium iodide in an aromatic solvent.
8. The. method of making an alkyldihydrothebainone which comprises reacting dihydrocodeinone with an alkyl magnesium bromide and an aromatic solvent.
9. The method of making an alkyldihydrothebainone which comprises reacting dihydrocodeinone with alkyl magnesium iodide and an aromatic solvent.
FRANK C. WHITMO-RE. AUGUST H. HOMEYER.
(References on following page) REFERENCES ormn OTfiER REFERENCES The following references are of record in the vLutz at ,1,: J. Am. Chem. Soc., vol. 57, pp. 265ifile of this patent: 2656 (1935).
' Sm 11 t 1.: J. .Ch .SOc., 1.58, .1457- UNITED STATES PATENTS 5 14 3 Au g. 1936) em v0 pp Gilman: Organic Chemistry (John Wiley New Number Name Date 2,178,010 Small et a1 Oct 31. 1939 York, 1938), vol. I, pp. 109, 110 and 556.
Fieser and Fieser: Organic Chemistry (D. C. 2'364'833 Wemard 1 10 Heath'& Co., 1944; Boston); p. 39 and p.803.
Claims (1)
- 6. THE METHOD OF MAKING METHYLDIHYDROTHEBAINONE WHICH COMPRISES ADDING A BENZENE SOLUTION OF DIHYDROCODEINONE TO A BENZENE SOLUTION OF A METHYL MAGNESIUM HALIDE SELECTED FROM THE GROUP CONSISTING OF A METHYL MAGNESIUM BROMIDE AND A METHYL MAGNESIUM IODIDE, DECOMPOSING THE COMPLEX FORMED BY ADDING EXCESS DILUTE HYDROCHLORIC ACID, EXTRACTING THE METHYLDIHYDROTHEBAINONE WITH CHLOROFORM, PURIFYING THE PRODUCT BY FORMING A HYDROHALIDE OF THE METHYLDIHYDROTHEBAINONE.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US667108A US2510731A (en) | 1946-05-03 | 1946-05-03 | Method of making alkyldihydrothebainones |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US667108A US2510731A (en) | 1946-05-03 | 1946-05-03 | Method of making alkyldihydrothebainones |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2510731A true US2510731A (en) | 1950-06-06 |
Family
ID=24676819
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US667108A Expired - Lifetime US2510731A (en) | 1946-05-03 | 1946-05-03 | Method of making alkyldihydrothebainones |
Country Status (1)
| Country | Link |
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| US (1) | US2510731A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2178010A (en) * | 1937-02-03 | 1939-10-31 | Small Lyndon Frederick | Nuclear substituted derivatives of the morphine series and methods for their preparation |
| US2364833A (en) * | 1941-12-06 | 1944-12-12 | Merck & Co Inc | N-allylnormorphine and processes for its production |
-
1946
- 1946-05-03 US US667108A patent/US2510731A/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2178010A (en) * | 1937-02-03 | 1939-10-31 | Small Lyndon Frederick | Nuclear substituted derivatives of the morphine series and methods for their preparation |
| US2364833A (en) * | 1941-12-06 | 1944-12-12 | Merck & Co Inc | N-allylnormorphine and processes for its production |
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