Water → (R)-4-(4-((4'-chlorobiphenyl-2-yl)(dimethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoic acid

HRID 1476332Notes

Reaction equation

[OH-].[Li+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C@H:16]([O:34][P:35]([O:39][CH3:40])([O:37][CH3:38])=[O:36])[CH:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:33]=[CH:32][C:26]([C:27]([O:29]CC)=[O:28])=[CH:25][CH:24]=3)[CH2:19][CH2:18]2)=[CH:6][CH:5]=1.C1COCC1.O>CO>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C@H:16]([O:34][P:35]([O:37][CH3:38])([O:39][CH3:40])=[O:36])[CH:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:33]=[CH:32][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=3)[CH2:19][CH2:18]2)=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 35 °C

Procedure

A mixture of lithium hydroxide (107 mg, 4.48 mmol), (R)-ethyl 4-(4-((4′-chlorobiphenyl-2-yl)(dimethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoate (INTERMEDIATE 121, 500 mg, 0.9 mmol), THF (10 ml), water (2.5 ml), and MeOH (2.5 ml) was heated at 35° C. overnight. The reaction mixture was concentrated under reduced pressure, diluted with water (10 ml) and acidified with an aqueous solution of 6 N HCl, resulting in a precipitate. The solid was collected by filtration to give the title compound (270 mg, yield: 57%). The title compound was used in the preparation of EXAMPLE 30 without further purification.

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
additiondiluted with water (10 ml)
customresulting in a precipitate
filtrationThe solid was collected by filtration

Sources & evidence

ORD record: ord-e194375ee018424d91e1e28d6771441c
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018381B2

Reaction notes

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