Lithium Hydroxide → 2-(difluoromethyl)-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carboxylic acid

HRID 44550Notes

Reaction equation

HRID 44550 reaction equation
[F:1][CH:2]([F:33])[C:3]1[N:7]([CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:19]=[C:20]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[CH:21]=[C:22]([C:23]([O:25]C)=[O:24])[C:5]=2[N:4]=1.[Li+].[OH-]>C1COCC1>[F:33][CH:2]([F:1])[C:3]1[N:7]([CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:19]=[C:20]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[CH:21]=[C:22]([C:23]([OH:25])=[O:24])[C:5]=2[N:4]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 66976872methyl 2-(difluoromethyl)-6-morpholino-1-(naphthalen-1-ylmethyl)-1H-benzo[d]imidazole-4-carboxylate

Product 1

HCID 569606842-(difluoromethyl)-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carboxylic acidYield 66.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture methyl 2-(difluoromethyl)-6-morpholino-1-(naphthalen-1-ylmethyl)-1H-benzo[d]imidazole-4-carboxylate (700 mg, 1.55 mmol) and 2N 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 to 3-4. Then a filtration was performed and the filter cake was collected, dried under vacuum to give the product (450 mg, 66%) as a white solid. 1H NMR (300 MHz, DMSO-d6,): δ ppm 3.07 (s, 4H), 3.68 (s, 4H, s), 6.20 (s, 2H), 6.30 (d, 1H, J=7.2 Hz), 7.20-7.72 (m, 6H), 7.85 (d, 1H, J=8.1 Hz), 8.01 (d, 1H, J=7.8 Hz), 8.24 (d, 1H, J=7.5 Hz); LC-MS: m/e=438 [M+1]+

Workup

  1. filtrationIt was filtered
  2. dissolutionthe filter cake was dissolved in water (10 mL)
  3. additionformic acid was added
  4. filtrationThen a filtration
  5. customthe filter cake was collected
  6. customdried under vacuum

Sources & evidence

ORD record
ord-a9d1f4353b664a7f96978e16519d79a4
Source dataset
uspto-grants-2013_09
Patent number
US08541411B2

Reaction notes

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