350801-68-2Relevant articles and documents
Method for synthesizing Pregabalin by taking chloroacetonitrile and isobutylaldehyde as raw materials
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Paragraph 0048; 0051, (2016/10/08)
The invention discloses a method for synthesizing Pregabalin by taking chloroacetonitrile and isobutylaldehyde as raw materials. The method comprises the steps: carrying out substitution reaction on chloroacetonitrile and trimethyl phosphite in a methanol solvent by taking sodium methoxide as a catalyst; carrying out substitution reaction on the substitution reaction product and 1-ethyl chloroacetate in an ethanol solvent by taking sodium hydroxide as a catalyst; carrying out Wittig-Horner reaction on the substitution reaction product and isobutylaldehyde in a THF solvent by taking sodium hydride as a catalyst; carrying out catalytic hydrogenation by taking Raney nickel as a catalyst; carrying out hydrolysis in a methanol solvent by taking potassium hydroxide as a catalyst, and then, adding acid into hydrolyzate for acid precipitation; and finally, carrying out chiral resolution by taking (S)-mandelic acid as a resolving agent. According to the method, chloroacetonitrile, which is cheap and is readily available, serves as a raw material and is subjected to substitution reaction twice, Wittig-Horner reaction with isobutylaldehyde, catalytic hydrogenation, hydrolyzing acid precipitation and chiral resolution, thereby obtaining Pregabalin. The reaction route is simple, and the yield of reaction of each step is relatively high, so that the total yield and purity of final Pregabalin are guaranteed.
An enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid via asymmetric hydrogenation
Burk, Mark J.,De Koning, Pieter D.,Grote, Todd M.,Hoekstra, Marvin S.,Hoge, Garrett,Jennings, Rex A.,Kissel, William S.,Le, Tung V.,Lennon, Ian C.,Mulhern, Thomas A.,Ramsden, James A.,Wade, Robert A.
, p. 5731 - 5734 (2007/10/03)
A concise enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid (1, Pregabalin) has been developed. The key step is the asymmetric hydrogenation of a 3-cyano-5-methylhex-3-enoic acid salt 2 with a rhodium Me-DuPHOS catalyst, providing the desired (S)-3-cyano-5-methylhexanoate 3 in very high ee. Subsequent hydrogenation of the nitrile 3 with a heterogeneous nickel catalyst provides Pregabalin I in excellent overall yield and purity.
