Lithium Hydroxide → 1-[(2-fluoro-3-methylphenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylic acid

HRID 44506Notes

Reaction equation

[F:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][N:10]1[C:14]2[CH:15]=[C:16]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[CH:17]=[C:18]([C:19]([O:21]C)=[O:20])[C:13]=2[N:12]=[C:11]1[CH3:29].[Li+].[OH-]>C1COCC1>[F:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][N:10]1[C:14]2[CH:15]=[C:16]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[CH:17]=[C:18]([C:19]([OH:21])=[O:20])[C:13]=2[N:12]=[C:11]1[CH3:29]

Participants

Conditions

Temperature: 45 °C

Procedure

A mixture of methyl 1-[(2-fluoro-3-methylphenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylate, prepared as described in Example 28 (240 mg, 0.6 mmol) and 2 N LiOH (1.8 mL, 3.6 mmol) in THF (20 mL), was stirred at 45° C. for 16 h. The solution was filtered; the filter cake was then dissolved in water (20 mL) and added into formic acid to adjust the pH of the solution to 3-4. Then a filtration was performed to provide the product (160 mg, 70%), as a white solid. 1H NMR (300 MJz, DMSO-d6): δ ppm 2.24 (d, 3H, J=1.8 Hz), 2.50 (s, 3H), 3.12 (t, 4H, J=4.8 Hz), 3.75 (t, 4H, J=4.8 Hz), 5.57 (s, 2H), 6.74 (t, 1H, J=7.5 Hz), 7.03 (t, 1H, J=7.5 Hz), 7.24 (t, 1H, J=7.5 Hz), 7.40 (d, 1H, J=2.4 Hz), 7.42 (d, 1H, J=2.4 Hz); LC-MS: m/e=384 [M+1]+

Workup

customprepared
filtrationThe solution was filtered
dissolutionthe filter cake was then dissolved in water (20 mL)
additionadded into formic acid
filtrationThen a filtration

Sources & evidence

ORD record: ord-7123a8b7fd7c401dae1056873d6b2ea4
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541411B2

Reaction notes

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