Phenol → N-(3,4-Dichlorophenyl)-4-{[(3S)-1-(2-phenoxyethyl)piperidin-3-yl]methyl}piperazine-1-carboxamide

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C@@H:19]3[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][OH:27])[CH2:20]3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].[C:28]1(O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.P(CCCC)(CCCC)CCCC>>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C@@H:19]3[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][O:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH2:20]3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

Reactant 3

HCID 996Phenol

HCID 13831Tributylphosphine

HCID 57656840N-(3,4-Dichlorophenyl)-4-{[(3S)-1-(2-hydroxyethyl)piperidin-3-yl]methyl}piperazine-1-carboxamide

Product 1

HCID 57656881N-(3,4-Dichlorophenyl)-4-{[(3S)-1-(2-phenoxyethyl)piperidin-3-yl]methyl}piperazine-1-carboxamideYield 21.5%

Procedure

N-(3,4-Dichlorophenyl)-4-{[(3S)-1-(2-hydroxyethyl)piperidin-3-yl]methyl}piperazine-1-carboxamide (250 mg, 0.62 mmols) and phenol (58.35 mg, 0.62 mmols) were stirred at room temperature under an atmosphere of argon before addition of P(Bu)3 (0.30 ml, 1.24 mmols) and 1,1-azodicarbonyl dipiperidine (312 mg, 1.24 mmols). This reaction mixture was stirred at room temperature overnight under an argon atmosphere. The reaction mixture was washed using brine and the organic layer dried (MgSO4) filtered then concentrated in vacuo onto silica gel (1 g). The resulting solid was subjected to chromatography on silica gel (20 g) using a gradient of 100% dichloromethane through to 20% methanolic ammonia in dichloromethane to give the title compound (65.4 mg).