Trimethyl phosphite → (R)-ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(dimethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoate

HRID 1476331Notes

Reaction equation

HRID 1476331 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C@H:14]([O:32][P:33]([O:38][CH2:39]C)([O:35][CH2:36]C)=[O:34])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:31]=[CH:30][C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)=[CH:4][CH:3]=1.ClC1C=CC(C2C=CC=CC=2[C@H](O)C2CCN(C3C=CC(C(OCC)=O)=CC=3)CC2)=CC=1.P(OC)(OC)OC>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C@H:14]([O:32][P:33]([O:35][CH3:36])([O:38][CH3:39])=[O:34])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:31]=[CH:30][C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 8472Trimethyl phosphiteHCID 56650671(R)-ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate2×HCID 58080102(R)-ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(diethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoate

Product 1

HCID 58080150(R)-ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(dimethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoateYield 67%

Procedure

A similar procedure to that described for INTERMEDIATE 119 utilizing (R)-ethyl 4-(4-((4′-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate (INTERMEDIATE 11A, 600 mg, 1.33 mmol) and trimethyl phosphite (0.473 ml, 4.0 mmol) as starting material was followed, with subsequent purification by column chromatography (ISCO, 0→100% EtOAc/hexane over 24 minutes) to give the title compound (500 mg, yield: 67%). The title compound was used in the preparation of INTERMEDIATE 122 without further purification.

Workup

  1. customwas followed, with subsequent purification by column chromatography (ISCO, 0→100% EtOAc/hexane over 24 minutes)

Sources & evidence

ORD record
ord-af0cbcf05a84433995ad246100734463
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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