Hydrochloric Acid → 6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-2-(trifluoromethyl)-1H-benzimidazole-4-carboxylic acid

HRID 1188826Notes

Reaction equation

HRID 1188826 reaction equation
[N:1]1([C:7]2[CH:8]=[C:9]([C:31]([O:33]C)=[O:32])[C:10]3[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[N:12]([CH2:19][C:20]4[C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[CH:23]=[CH:22][CH:21]=4)[C:11]=3[CH:30]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[OH-].[Na+].Cl>CO>[N:1]1([C:7]2[CH:8]=[C:9]([C:31]([OH:33])=[O:32])[C:10]3[N:14]=[C:13]([C:15]([F:18])([F:16])[F:17])[N:12]([CH2:19][C:20]4[C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[CH:23]=[CH:22][CH:21]=4)[C:11]=3[CH:30]=2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 56960267methyl 6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-2-(trifluoromethyl)-1H-benzimidazole-4-carboxylate

Product 1

HCID 569601306-(4-morpholinyl)-1-(1-naphthalenylmethyl)-2-(trifluoromethyl)-1H-benzimidazole-4-carboxylic acidYield 82%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension of methyl 6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-2-(trifluoromethyl)-1H-benzimidazole-4-carboxylate, prepared as described in Example 48 (1.28 g, 2.73 mmol) in Methanol (18 mL) and 1 M sodium hydroxide (15 mL, 15.00 mmol) was stirred overnight at rt, then at 50° C. for 5 h. The reaction was cooled to room temperature and acidified (pH 4) by the addition of 1 N HCl. The precipitate formed was collected by filtration, washed with water and dried to give the desired product (1.13 g, 2.233 mmol, 82% yield). A portion of this material (132 mg) was purified by reverse phase-HPLC (15-95% AcCN in water plus 0.1% TFA). The fractions containing product were combined and the volume was reduced to about ⅓ of the original. The precipitate formed was collected, washed with water and dried in a vacuum oven (50° C., overnight) to give the desired product (88.4 mg, 0.194 mmol, 7.12% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.11 (br. s., 1H), 8.26 (d, J=8.59 Hz, 1H), 8.01 (d, J=7.33 Hz, 1H), 7.85 (d, J=8.34 Hz, 1H), 7.57-7.73 (m, 3H), 7.35 (d, J=2.53 Hz, 1H), 7.29-7.34 (m, 1H), 6.24 (d, J=7.07 Hz, 1H), 6.22 (s, 2H), 3.64-3.72 (m, 4H), 3.06-3.18 (m, 4H). MS (ES+) m/e 456 [M+H]+.

Workup

  1. customprepared
  2. waitat 50° C. for 5 h
  3. temperatureThe reaction was cooled to room temperature
  4. customThe precipitate formed
  5. filtrationwas collected by filtration
  6. washwashed with water
  7. customdried

Sources & evidence

ORD record
ord-68da48269a0f441695662bdf8b0e31ff
Source dataset
uspto-grants-2014_03
Patent number
US08674090B2

Reaction notes

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