Lithium Hydroxide → 4-{4-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-azepan-1-yl}-benzoic acid

HRID 1689792Notes

Reaction equation

[OH-].[Li+].C([O:5][C:6](=[O:38])[C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:19][CH2:18][CH2:17][CH:16]([O:20][CH2:21][C:22]3[C:23]([C:30]4[C:35]([Cl:36])=[CH:34][CH:33]=[CH:32][C:31]=4[Cl:37])=[N:24][O:25][C:26]=3[CH:27]3[CH2:29][CH2:28]3)[CH2:15][CH2:14]2)=[CH:9][CH:8]=1)C>O1CCOCC1>[CH:27]1([C:26]2[O:25][N:24]=[C:23]([C:30]3[C:31]([Cl:37])=[CH:32][CH:33]=[CH:34][C:35]=3[Cl:36])[C:22]=2[CH2:21][O:20][CH:16]2[CH2:17][CH2:18][CH2:19][N:13]([C:10]3[CH:9]=[CH:8][C:7]([C:6]([OH:38])=[O:5])=[CH:12][CH:11]=3)[CH2:14][CH2:15]2)[CH2:29][CH2:28]1

Participants

Conditions

Temperature: 90 °C

Procedure

A solution 2M of lithium hydroxide (283 μL, 566 μmoles) is added to a solution of 4-{4-[5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-azepan-1-yl}-benzoic acid ethyl ester (isomer A, 60 mg, 113 μmoles) in 1,4-dioxane (2 mL) and the mixture is stirred at 90° C. overnight. The organic solvent is removed and HCl (1M) is added until the solution reaches pH 3-4. The solid is filtered and purified via flash chromatography (12 g silica) eluting with a gradient of dichloromethane:ethyl acetate from 10% to 20% to provide the title compound (50 mg, 88%) as a white solid. ES/MS m/z 501.0 (M+1).

Workup

customThe organic solvent is removed
additionHCl (1M) is added until the solution
filtrationThe solid is filtered
custompurified via flash chromatography (12 g silica)
washeluting with a gradient of dichloromethane

Sources & evidence

ORD record: ord-0f456872bf78459789e215b694631eae
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153624B2

Reaction notes

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