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

HRID 2371175Notes

Reaction equation

HRID 2371175 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-7b2a27072ad94a7ca768c5a7dff1fe30
Source dataset
uspto-grants-2014_04
Patent number
US08710224B2

Reaction notes

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