Method for producing pyrrolidine compound
The present invention provides a production method suitable for industrial production of (2S,3S)-3-amino-2-(3-bromo-2-fluorobenzyl)pyrrolidine having a protecting group at the 1-position. The present invention is a method for producing N-[(4-methylphenyl)sulfonyl]-L-phenylalanine salt of (2S,3S)-3-amino-2-(3-bromo-2-fluorobenzyl)pyrrolidine having a protecting group at the 1-position, which comprises Step 2: a step of subjecting 2-(3-bromo-2-fluorobenzyl)-3-(methoxyimino)pyrrolidine having a protecting group at the 1-position to a reduction reaction; and Step 3: a step of subjecting the product obtained in Step 2 to optical resolution using salt formation with N-[(4-methylphenyl)sulfonyl]-L-phenylalanine.
1 . A method for producing N-[(4-methylphenyl)sulfonyl]-L-phenylalanine salt of (2S,3S)-3-amino-2-(3-bromo-2-fluorobenzyl)pyrrolidine having a protecting group at the 1-position, which comprises
subjecting 2-(3-bromo-2-fluorobenzyl)-3-(methoxyimino)pyrrolidine having a protecting group at the 1-position to a reduction reaction; and
subjecting the product to optical resolution using salt formation with N-[(4-methylphenyl)sulfonyl]-L-phenylalanine.
2 . The method according to claim 1 , wherein the reduction reaction is carried out in the presence of zirconium(IV) chloride.
3 . A method for producing N-[(4-methylphenyl)sulfonyl]-L-phenylalanine salt of (2S,3S)-3-amino-2-(halo-substituted benzyl)pyrrolidine having a protecting group at the 1-position, which comprises
subjecting 2-(halo-substituted benzyl)-3-(methoxyimino)pyrrolidine having a protecting group at the 1-position to a reduction reaction; and
subjecting the product to optical resolution using salt formation with N-[(4-methylphenyl)sulfonyl]-L-phenylalanine.
4 . The method according to claim 3 , wherein the reduction reaction is carried out in the presence of zirconium(IV) chloride.
5 . The method of claim 3 further comprising reacting 2-(halo-substituted benzyl)-3-oxopyrrolidine having a protecting group at the 1-position with O-methylhydroxylamine or a salt thereof to provide 2-(halo-substituted benzyl)-3-(methoxyimino)pyrrolidine.