Lithium Hydroxide → 6-(4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic acid

HRID 1689790Notes

Reaction equation

[OH-].[Li+].C[O:4][C:5]([C:7]1[C:15]2[C:10](=[CH:11][C:12]([N:16]3[CH2:21][CH2:20][CH:19]([O:22][CH2:23][C:24]4[C:25]([C:32]5[C:37]([Cl:38])=[CH:36][CH:35]=[CH:34][C:33]=5[Cl:39])=[N:26][O:27][C:28]=4[CH:29]4[CH2:31][CH2:30]4)[CH2:18][CH2:17]3)=[CH:13][CH:14]=2)[N:9]([CH3:40])[CH:8]=1)=[O:6]>O1CCOCC1>[CH:29]1([C:28]2[O:27][N:26]=[C:25]([C:32]3[C:33]([Cl:39])=[CH:34][CH:35]=[CH:36][C:37]=3[Cl:38])[C:24]=2[CH2:23][O:22][CH:19]2[CH2:20][CH2:21][N:16]([C:12]3[CH:11]=[C:10]4[C:15]([C:7]([C:5]([OH:6])=[O:4])=[CH:8][N:9]4[CH3:40])=[CH:14][CH:13]=3)[CH2:17][CH2:18]2)[CH2:30][CH2:31]1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 2M lithium hydroxide (1.2 mL, 2.46 mmol) is added to a solution of 6-{4-[5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid methyl ester (195 mg, 351.7 μmoles) in 1,4-dioxane (5 mL) and the mixture is stirred at 80° C. overnight. The organic solvent is removed and HCl (1M) is added until the solution reaches pH 3-4. The solid is filtered and washed with water and acetonitrile to provide the title compound (165 mg, 87%) as a white solid. ES/MS m/z 540.0 (M+1).

Workup

customThe organic solvent is removed
additionHCl (1M) is added until the solution
filtrationThe solid is filtered
washwashed with water and acetonitrile

Sources & evidence

ORD record: ord-2a37668c047540f09003e24b503411c2
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153624B2

Reaction notes

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