Lithium Hydroxide → (1R,3S)-3-((S)-2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazine-1-carbonyl)cyclopentanecarboxylic acid

HRID 1423145Notes

Reaction equation

HRID 1423145 reaction equation
C[O:2][C:3]([C@@H:5]1[CH2:9][CH2:8][C@H:7]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH:19]=3)[CH2:14][C@@H:13]2[CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:11])[CH2:6]1)=[O:4].[Li+].[OH-]>>[CH2:32]([C@H:13]1[CH2:14][N:15]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH:27]3[CH2:28][CH2:29][CH2:30][CH2:31]3)[CH:19]=2)[CH2:16][CH2:17][N:12]1[C:10]([C@H:7]1[CH2:8][CH2:9][C@@H:5]([C:3]([OH:4])=[O:2])[CH2:6]1)=[O:11])[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

3

Reactant 2

HCID 3939Lithium HydroxideHCID 67291269(1R,3S)-3-[(S)-2-Benzyl-4-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine-1-carbonyl]-cyclopentanecarboxylic acid methyl ester

Product 1

HCID 52918655(1R,3S)-3-((S)-2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazine-1-carbonyl)cyclopentanecarboxylic acidYield 80%

Procedure

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.

Workup

  1. customLC/MS (Method B) 4.14 min, [M+1]+ 521

Sources & evidence

ORD record
ord-286eb0c698584551be2ec5f670569664
Source dataset
uspto-grants-2015_01
Patent number
US08927546B2

Reaction notes

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