Abstract

The present invention relates to a preparation method for an aprepitant intermediate impurity. The preparation method comprises the following reaction steps: (A) carrying out a Grignard reaction on a raw material 1 and a Grignard reagent 4-fluorophenylmagnesium halide; (B) carrying out a reduction reaction on a reaction product obtained in step (A) and a reducing agent to obtain a compound 4; (C) carrying out a debenzylation reaction on the obtained compound 4 and a deprotection reagent to obtain a crude product 5; (D) reacting the obtained crude product 5 with a protective reagent in the presence of a solvent and an alkali to obtain a compound 6; and (E) carrying out a deprotection reaction on the obtained compound 6 and an acid or alkali in the presence of a solvent, and carrying out separation and purification to obtain a refined product 5. According to the method, the compound 4 is obtained by means of the reduction reaction, and then undergoes the debenzylation reaction to synthesize the compound 5, so the compound 5 can be successfully synthesized, and the yield and purity of the crude product 5 are greatly improved. Furthermore, the crude product 5 reacts with the protective reagent and is purified to obtain the compound 6, and the compound 6 is subjected to the deprotection reaction, and then is separated by means of conventional column chromatography to obtain the high-purity compound 5.

IPC Classes  ?

• C07C 213/00 - Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
• C07C 217/10 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical containing six-membered aromatic rings

Abstract

Disclosed in the present invention is a (S)1-phenyl-1,2,3,4-tetrahydroisoquinoline synthesis method, comprising the following steps: 1) dissolving raw material 1 in a solvent, and adding an alkali and a catalyst; and 2) carrying out gas replacement by using hydrogen to form a hydrogen atmosphere, and carrying out a pressurization reaction to obtain (S)1-phenyl-1,2,3,4-tetrahydroisoquinoline 2, wherein the catalyst is a BIAMH system catalyst, a D-BIMAH system catalyst, or a P-BIMAH system catalyst.

IPC Classes  ?

• C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines