Dicyclohexylcarbodiimide → (1R,3S)-3-[(S)-2-Benzyl-4-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine-1-carbonyl]-cyclopentanecarboxylic acid methyl ester

Participants

Reaction Steps

A solution of (S)-3-Benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine (92 mg, 0.25 mmol) in CH2Cl2 (1 mL) at 0-5° C. was treated with a catalytic amount of DMAP and (1S,3R)-3-(methoxycarbonyl)cyclopentanecarboxylic acid (47 mg, 0.28 mmol) followed by DCC (57 mg, 0.28 mmol). The reaction mixture was allowed to warm to room temperature and stir 1 h. After this time the reaction mixture was evaporated and the residue purified by silica gel flash chromatography with 30% then 50% EtOAc/hexanes as eluant to afford intermediate (1R,3S)-3-[(S)-2-Benzyl-4-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine-1-carbonyl]-cyclopentanecarboxylic acid methyl ester as an oil (109 mg, 84%). LC/MS (Method B) 4.14 min, [M+1]+ 521. The intermediate (1R,3S)-3-[(S)-2-Benzyl-4-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine-1-carbonyl]-cyclopentanecarboxylic acid methyl ester was then hydrolyzed with LiOH as described in Example 121, to afford the title compound as a colorless solid (85 mg, 80%) LC/MS (Method B) 3.68 min, [M+1]+ 507.

Provenance & Evidence