Acetic Acid → HCID 24986434, compound

HRID 1665230Notes

Reaction equation

HRID 1665230 reaction equation
[Cl:1][C:2]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([Cl:28])[C:3]=1[CH2:4][C:5]1[N:9]([CH3:10])[C:8]2[C:11]([C:15]([CH2:18][CH3:19])=[CH:16][CH3:17])=[CH:12][CH:13]=[CH:14][C:7]=2[N:6]=1.[C:29]([OH:32])(=[O:31])[CH3:30].C(=O)(O)[O-].[Na+].ClC1C=C(C(F)(F)F)C=C(Cl)C=1CC1N(C)C2C(C(CC)C(O)C)=CC=CC=2N=1>O1CCCC1>[C:29]([O:32][CH:16]([CH3:17])[CH:15]([C:11]1[C:8]2[N:9]([CH3:10])[C:5]([CH2:4][C:3]3[C:2]([Cl:1])=[CH:23][C:22]([C:24]([F:27])([F:26])[F:25])=[CH:21][C:20]=3[Cl:28])=[N:6][C:7]=2[CH:14]=[CH:13][CH:12]=1)[CH2:18][CH3:19])(=[O:31])[CH3:30]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 24986435HCID 24986435, compoundHCID 67438838HCID 67438838, compound

Product 1

HCID 24986434HCID 24986434, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-[2,6-dichloro-4-(trifluoromethyl)benzyl]-7-[1-ethylprop-1-en-1-yl]-1-methyl-1H-benzimidazole (60 mg, 0.141 mmol) in tetrahydrofuran (1.5 mL) was added a solution of borane-dimethyl sulfide complex in tetrahydrofuran (1.9 M, 1.5 mL, 2.81 mmol) at 0° C. After the reaction mixture was stirred at room temperature for 15 hr, acetic acid (3.0 mL) was added thereto and the mixture was heated at 120° C. for 2 hr. After cooling, the mixture was poured into saturated aqueous sodium bicarbonate solution (50 mL) and extracted with ethyl acetate (50 mL, twice). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 5-50% ethyl acetate/n-hexane gradient mixture to give 2-{2-[2,6-dichloro-4-(trifluoromethyl)benzyl]-1-methyl-1H-benzimidazol-7-yl}-1-methylbutyl acetate (17 mg, 0.0349 mmol, 25%) and 3-{2-[2,6-dichloro-4-(trifluoromethyl)benzyl]-1-methyl-1H-benzimidazol-7-yl}pentan-2-ol (less polar diastereomer; 2.4 mg, 0.00539 mmol, 4%, more polar diastereomer; 2.5 mg, 0.00562 mmol, 4%).

Workup

  1. temperaturethe mixture was heated at 120° C. for 2 hr
  2. temperatureAfter cooling
  3. extractionextracted with ethyl acetate (50 mL
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with 5-50% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-18f6caa207b84b37b7e65eac73572eef
Source dataset
uspto-grants-2011_10
Patent number
US08039500B2

Reaction notes

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