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

HRID 603218Notes

Reaction equation

HRID 603218 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

4

Reactant 3

HCID 996PhenolHCID 13831TributylphosphineHCID 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).

Workup

  1. washThe reaction mixture was washed
  2. dry with materialthe organic layer dried (MgSO4)
  3. filtrationfiltered
  4. concentrationthen concentrated in vacuo onto silica gel (1 g)

Sources & evidence

ORD record
ord-b6a80f8cf5e44f0e8ba3b32981360625
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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