Crystal of pyrrole derivative and method for producing the same

A method for producing (S)-1-(2-hydroxyethyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide represented by the following formula (A):

• characterized by obtaining one atropisomer of (RS)-1-(2-hydroxyethyl)-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxylic acid represented by the following formula (Ia):
• by resolution using an optically active amine having a cinchonine skeletal formula, removing the optically active amine under acidic conditions, followed by reaction with oxalyl chloride, thereby forming the following intermediate compound (IIa):
• and then further reacting the intermediate compound (IIa) with 4-(methylsulfonyl)aniline, thereby forming the following intermediate compound (IIIa):
• followed by a base treatment.

A method for making (RS)-1-(2-hydroxyethyl)-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxylic acid having the structure:

• comprising:
• (a) N-alkylating ethyl 2-chloro-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxylate with ethylene carbonate to provide ethyl (RS)-2-chloro-1-(2-hydroxyethyl)-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxylate having the structure:
• (b) dechlorinating ethyl (RS)-2-chloro-1-(2-hydroxyethyl)-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxylate to provide ethyl (RS)-1-(2-hydroxyethyl)-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxylate having the structure:
• and
• (c) hydrolyzing ethyl (RS)-1-(2-hydroxyethyl)-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxylate to provide (RS)-1-(2-hydroxyethyl)-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxylic acid.