ChemicalBook CAS DataBase List Captopril

Captopril synthesis

11synthesis methods

Product Name:Captopril
CAS Number:62571-86-2
Molecular formula:C9H15NO3S
Molecular Weight:217.29

Captopril, 1-[(2S)-3-mercapto-2-methylpropionyl]-L-proline (22.7.4), is synthesized by direct acylation of L-proline with 3-acetylthio-2-methylpropionic acid chloride (22.7.2), which is synthesized from 3-acetylthio-2-methylpropionic acid (22.7.1), which is in turn synthesized by reacting methacrylic and thioacetic acid. 1-(3-Acetylthio-2-Dmethylpropanoyl)- L-proline (22.7.3) is formed by reacting L-proline with 3-acetylthio-2- methylpropionic acid chloride, and it undergoes further ammonolysis with ammonia, to give the desired captopril (22.7.4).

(R)-3-(ACETYLTHIO)-2-METHYLPROPIONYL CHLORIDE

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147-85-3 Synthesis

147-85-3
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62571-86-2
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Yield:62571-86-2 93%

Reaction Conditions:

with sodium hydroxide in water at -2 - 40; pH=8 - 10; for 4.66667 h;

Steps:

2.4; 2.5 4. Preparation of free acid

60 ml of purified water and 10 g of L-valine were added to a 250 ml reaction flask.Stir and dissolve, add sodium hydroxide solution(7.2 g sodium hydroxide + 70 ml water) to pH = 8 to 10, and cooled to -2 °C.Drop 15.5g L-acid chloride, temperature control 0 ~ 5 ° C, the sameAdd the above sodium hydroxide solution dropwise to make PH=8~10, drop,The reaction was carried out for 10 minutes, and the pH was measured again. Rose to 25 ~ 30 ° C,Reaction for 3 hours. At the end of the reaction, adjust the pH = 1 to 2 with concentrated hydrochloric acid.Extracted twice with 100 x 2 ml of ethyl acetate.Combine organic phases and concentrateObtained 21.2g of free acid,The yield was 95%.5. Preparation of LL-captoprilIn a 250 ml reaction flask, 14 g of sodium hydroxide and 30 ml of purified water were added.Stir and dissolve, and cool to -2 to 0 °C. Add 21g of free acid and feed it.The temperature was raised to 35 to 40 ° C for 1.5 hours. After the reaction is over,Cool down to 25 ~ 30 ° C, adjust the pH = 1 ~ 2 with concentrated hydrochloric acid, add 0.5g zinc powder 14 Stir for 1 hour. After the reaction was completed, it was filtered.The filtrate was extracted twice with 100 x 2 ml of dichloromethane and the organic phases were combined.Dry over anhydrous magnesium sulfate, filter,Concentrated to LD-captopril 16.4g,The yield was 93%.

References:

CN109608378,2019,A Location in patent:Paragraph 0032; 0040; 0041; 0042; 0043

613256-52-3 Synthesis