Dichloromethane → HCID 11485088, compound

Participants

Reaction Conditions

Reaction Steps

(2R)-1-Acetoxy-2-acetylamino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)-1-(4-(3,4-dimethylphenyl)butanoyloxy)but-1-enyl]pyrrol-2-yl}butane (29.6 g, 48.1 mmol) obtained in Example 2 (2a) was dissolved in a mixture of tetrahydrofuran (100 mL) and methanol (100 mL), and water (100 mL) and lithium hydroxide monohydrate (20.2 g, 481 mmol) were added thereto, followed by stirring of the mixture at 60° C. for 5 hours. After cooling, water and methylene chloride were added to the reaction mixture to separate it. An organic phase was separated and after it was washed with a saturated aqueous NaCl solution, it was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by basic silica gel (NH type) chromatography (methylene chloride:methanol, 100:1) to obtain (2R)-2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol (13.2 g, yield: 77%). A solution of fumaric acid (244 g, 2.10 mmol) in methanol (5 mL) was added to a solution of the obtained (2R)-2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol (1.50 g, 4.21 mmol) in methanol (16 mL) under ice-cooling. After methanol was evaporated under reduced pressure, the residue was dissolved in a small amount of methanol, ethyl acetate was added thereto and recrystallization was carried out to obtain a crude crystal (1.51 g) of the title compound. The obtained crude crystal (1.51 g), was subjected again to recrystallization using methanol and ethyl acetate to obtain the title compound (1.23 g, yield: 71%) as a white crystal.

Provenance & Evidence