CN104402745A - Method for synthesizing isopropyl 3-aminocrotonate - Google Patents

Abstract

The invention discloses a method for synthesizing isopropyl 3-aminocrotonate. The method comprises the following steps of using a ketene dimer as a raw material, condensing the ketene dimer and isopropyl alcohol under the action of catalysts so as to obtain isopropyl acetoacetate, and then performing a reaction on the isopropyl acetoacetate and ammonia gas so as to obtain the isopropyl 3-aminocrotonate. The isopropyl 3-aminocrotonate synthesized by the method disclosed by the invention is good in quality, is high in yield, is simple in preparation method, is low in energy consumption and is low in cost.

Description

The synthetic method of the amino β-crotonic acid isopropyl ester of a kind of 3-

 

Technical field

The present invention relates to a kind of preparation method of pharmaceutical raw material, specifically the synthetic method of the amino β-crotonic acid isopropyl ester of a kind of 3-.

Background technology

The amino β-crotonic acid isopropyl ester of 3-, colourless-micro-yellow clear liquid, become white-micro-yellow crystal after cooling, fusing point is 19-23 DEG C, boiling point 80 DEG C/133Pa, relative density 0.996, refractive index 1.4940, flash-point 92 DEG C.The amino β-crotonic acid isopropyl ester of 3-is the important intermediate of synthesis peripheral vasodilation and hypotensor nimodipine (Nimodipine).

Summary of the invention

The technical problem to be solved in the present invention is to provide the synthetic method of the amino β-crotonic acid isopropyl ester of a kind of 3-, and its synthetic method is simple, and yield is high.

Technical scheme of the present invention is:

A synthetic method for the amino β-crotonic acid isopropyl ester of 3-, comprises the steps:

(1), first Virahol and triethylamine are put into reflux in reaction vessel, then ketene dimer is dripped, ketene dimer has reacted rear cool to room temperature and has washed layering, wherein organic layer washing, concentrated, simple distillation collection cut, i.e. ISOPROPYL ACETOACETATE;

(2), the ISOPROPYL ACETOACETATE that step (1) obtains is joined in reaction vessel, pass into excess of ammonia gas under room temperature, have solid to separate out after cooling, then filtering reacting liquid, filtration cakes torrefaction, obtain 3-amino β-crotonic acid isopropyl ester product.

The mass ratio of described ketene dimer, Virahol, triethylamine is 1: 1.1-1.2:0.002-0.0025.

Described ISOPROPYL ACETOACETATE, the mass ratio of ammoniacal liquor are 1: 0.13-0.14.

Washing layering in described step (1) select mass percent be 10% sodium carbonate solution washing layering, organic layer is again with water washing twice.

Advantage of the present invention:

3-prepared by the present invention amino β-crotonic acid isopropyl ester quality is good, and yield is high, and preparation method is simple, and less energy consumption, cost is low.

Embodiment

A synthetic method for the amino β-crotonic acid isopropyl ester of 3-, comprises the steps:

(1), first 120ml Virahol and 0.2g Triethylamine catalyst are put into reflux in 250ml four-hole boiling flask, then ketene dimer 84g altogether is slowly dripped, for reacting fully, drip off the longer return time of rear maintenance, last GC detects ketene dimer and has reacted rear cool to room temperature, add the sodium carbonate solution washing layering that mass percent is 10%, organic layer is again with after water washing twice, concentrate and boil off the complete raw material of most of unreacted, simple distillation collects boiling point 75-76 DEG C/2kPa cut, obtain 115g product, ISOPROPYL ACETOACETATE content about 98%, yield 80%,

(2), the ISOPROPYL ACETOACETATE that 72g step (1) obtains is joined in 250ml four-hole boiling flask, pass into 10g ammonia under room temperature, after cooling, have solid to separate out, then filtering reacting liquid, filtration cakes torrefaction, obtains 3-amino β-crotonic acid isopropyl ester off-white color solid phase prod, yield 80%; Detection level, determines structure.

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Claims (4)

1. a synthetic method for the amino β-crotonic acid isopropyl ester of 3-, is characterized in that, comprise the steps:

(1), first Virahol and triethylamine are put into reflux in reaction vessel, then ketene dimer is dripped, ketene dimer has reacted rear cool to room temperature and has washed layering, wherein organic layer washing, concentrated, simple distillation collection cut, i.e. ISOPROPYL ACETOACETATE;

(2), the ISOPROPYL ACETOACETATE that step (1) obtains is joined in reaction vessel, pass into excess of ammonia gas under room temperature, have solid to separate out after cooling, then filtering reacting liquid, filtration cakes torrefaction, obtain 3-amino β-crotonic acid isopropyl ester product.

2. the synthetic method of the amino β-crotonic acid isopropyl ester of a kind of 3-according to claim 1, is characterized in that: the mass ratio of described ketene dimer, Virahol, triethylamine is 1: 1.1-1.2:0.002-0.0025.

3. the synthetic method of the amino β-crotonic acid isopropyl ester of a kind of 3-according to claim 1, is characterized in that: described ISOPROPYL ACETOACETATE, the mass ratio of ammoniacal liquor are 1: 0.13-0.14.

4. the synthetic method of the amino β-crotonic acid isopropyl ester of a kind of 3-according to claim 1, is characterized in that: the washing layering in described step (1) select mass percent be 10% sodium carbonate solution washing layering, organic layer is again with water washing twice.