CN102702183A - New synthesis process of 3-isopropyl-(1,2,4)oxadiazol-5-piperidine-1-carbonyl tertbutyl ester compounds - Google Patents

Abstract

The invention discloses a new synthesis process of 3-isopropyl-(1,2,4)oxadiazol-5-piperidine-1-carbonyl tertbutyl ester compounds, effectively solving the disadvantages of the previously reported process, such as troublesome aftertreatment, high cost and relatively low yield. The new two-step reaction synthesis process comprises the steps of reacting material cyano group with hydroxyamino, and directly reacting with acid through a one-pot method. The whole process is easy to operate, the aftertreatment is simple, and the yield is greatly improved.

Description

New Synthesis Process of 3-Isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl Ester

technical field

The invention relates to a new synthesis process of 3-isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl ester compounds, belonging to the technical fields of medicine and chemical industry.

Background technique

Isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl ester compounds are important chemical intermediates, which are widely used in the fields of medicine and pesticides, and their synthetic routes are currently reported Mostly, the raw material cyano group first reacts with hydroxylamine, then condenses with acid and then heats and dehydrates to obtain the target product. The specific route is as follows:

The above-mentioned route needs to be condensed and reacted to form an amide first, and then dehydrated and ring-closed, which has the disadvantages of cumbersome post-treatment, high cost, and low yield.

Contents of the invention

The present invention aims at the deficiencies of 3-isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl ester compound in the previous synthetic method, which are cumbersome post-treatment, high cost, low yield, etc. , invented the two-step reaction with raw material cyano group and hydroxylamine, and then directly reacted with acid in one pot, so that the whole process is easy to operate, the post-treatment is simple, and the yield is greatly improved.

The 3-isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl ester compound is synthesized, the raw material cyano group includes but not limited to acetonitrile, n-propionitrile, iso Acrylonitrile, tert-butyronitrile, isobutyronitrile, n-butyronitrile, n-valeronitrile, isovaleronitrile, n-capronitrile, etc.

The 3-isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl ester compound is synthesized, and the raw materials include but not limited to 4-carbonyl tert-butyl ester-1 Formic acid, acetic acid, propionic acid, cyclopropionic acid, n-butyric acid, cyclobutanoic acid, cyclopentanoic acid, etc.

The 3-isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl ester compound is synthesized from (2) and (3) one-pot reaction solutions including but not limited to Toluene, xylene, benzene, dioxane, 1,2-dichloroethane, etc.

The 3-isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl ester compound is synthesized by (2) and (3) one-pot reaction temperature including but not limited to 0 Celsius to 200 Celsius.

The 3-isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl ester compound is synthesized by a one-pot method, without purification in the middle, and finally unified treatment.

The above-mentioned chemical reaction scheme with cyano group as starting material is as follows:

Detailed ways

Preparation of compound (2):

Dissolve 138 grams (2 moles) of starting material (1) in 1.4 liters of anhydrous methanol, add 152 grams (2.2 moles) of hydroxylamine hydrochloride, add 88 grams (2.2 moles) of sodium hydroxide in batches under ice-water cooling, and complete the addition After stirring overnight at room temperature, the methanol was distilled off, the residue was poured into 1 liter of ice water, extracted with ethyl acetate (500 ml*4), washed with saturated brine (500 ml), dried over anhydrous sodium sulfate, filtered, and spin-dried. 173 g (yield 85%) of white solid were obtained.

One-pot preparation of compound (5):

102 grams (1 mole) of the newly prepared compound (2) was dissolved in 1 liter of toluene solution, and 229 grams (1 mole) of 4-carbonyl tert-butyl ester-1-piperidine acid was added, and after the addition was completed, reflux and stirred for 24 hours, and cooled A catalytic amount of p-toluenesulfonic acid (1 g) was added and refluxed for 24 hours, spin-dried, and recrystallized from ethyl acetate to obtain 236 g of the target product (yield 80%).

Claims (5)

1. The synthesis of the 3-isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl ester compound, the raw material cyano group includes but not limited to acetonitrile, n-propionitrile , Isopropyl nitrile, tert-butyronitrile, isobutyronitrile, n-butyronitrile, n-valeronitrile, isovaleronitrile, n-capronitrile and so on. 2. Synthesis of the 3-isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl ester compound, the raw acid includes but not limited to 4-carbonyl tert-butyl ester -1 Formic acid, acetic acid, propionic acid, cyclopropionic acid, n-butyric acid, cyclobutanoic acid, cyclopentanoic acid, etc. 3. The 3-isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl ester compound is synthesized by (2) and (3) one-pot reaction solution containing but Not limited to toluene, xylene, benzene, dioxane, 1,2-dichloroethane, etc. 4. The 3-isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl ester compound is synthesized by (2) and (3) one-pot reaction temperature including but not only Limited to 0°C to 200°C. 5. The 3-isopropyl-(1,2,4)oxadiazole-5-piperidine-1-carbonyl tert-butyl ester compound is synthesized by a one-pot method, without purification in the middle, and finally unified treatment.