Lithium Hydroxide → 2-(difluoromethyl)-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylic acid

HRID 44552Notes

Reaction equation

[F:1][CH:2]([F:34])[C:3]1[N:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[C:10]=2[CH3:19])[C:6]2[CH:20]=[C:21]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[CH:22]=[C:23]([C:24]([O:26]C)=[O:25])[C:5]=2[N:4]=1.[Li+].[OH-]>C1COCC1>[F:34][CH:2]([F:1])[C:3]1[N:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:16])[F:17])[C:10]=2[CH3:19])[C:6]2[CH:20]=[C:21]([N:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[CH:22]=[C:23]([C:24]([OH:26])=[O:25])[C:5]=2[N:4]=1

Participants

Conditions

Temperature: 45 °C

Procedure

A mixture of methyl 2-(difluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazole-4-carboxylate (700 mg, 1.45 mmol) and 2 N LiOH (5 mL) in THF (10 mL) was stirred at 45° C. for 4 h. It was filtered, the filter cake was dissolved in water (10 mL) and formic acid was added to adjust pH=3-4. Then a filtration was performed and the filter cake was dried under vacuum to give the desired product (400 mg, 59%) as a white solid. 1H NMR (300 MHz, DMSO-d6): δ ppm 2.53 (s, 3H), 3.13 (s, 4H), 3.73 (s, 4H), 5.75 (s, 2H), 6.29 (d, 1H, J=7.5 Hz), 7.19-7.61 (m, 5H), 12.97 (br s, 1H); LC-MS: m/e=470 [M+1]+

Workup

filtrationIt was filtered
dissolutionthe filter cake was dissolved in water (10 mL)
additionformic acid was added
filtrationThen a filtration
customthe filter cake was dried under vacuum

Sources & evidence

ORD record: ord-e9076e70411d49e1b7d422bd1f38bf45
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541411B2

Reaction notes

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