Diethyl Ether → 2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-N-methyl-1H-benzimidazol-5-amine

HRID 472949Notes

Reaction equation

HRID 472949 reaction equation
[C:1]([C:5]1[N:9]([CH2:10][CH:11]2[CH2:16][CH2:15][C:14]([F:18])([F:17])[CH2:13][CH2:12]2)[C:8]2[CH:19]=[CH:20][C:21]([NH:23][C:24](=O)OC)=[CH:22][C:7]=2[N:6]=1)([CH3:4])([CH3:3])[CH3:2].CCOCC.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[C:1]([C:5]1[N:9]([CH2:10][CH:11]2[CH2:16][CH2:15][C:14]([F:17])([F:18])[CH2:13][CH2:12]2)[C:8]2[CH:19]=[CH:20][C:21]([NH:23][CH3:24])=[CH:22][C:7]=2[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 21226445Aluminium lithium hydrideHCID 57723214Methyl {2-tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}carbamate

Product 1

HCID 574410772-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-N-methyl-1H-benzimidazol-5-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Methyl {2-tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}carbamate (115 mg, 0.303 mmol) was dissolved in 10 mL of THF at 0° C. 1M Ha/ether (0.425 mL, 0.424 mmol) was added and the solution was stirred at 0° C. for 15 min. LiAlH4 (57 mg, 1.52 mmol) was added slowly and the solution was stirred at rt overnight. The reaction was quenched at 0° C. by the addition of MeOH (1 mL) and water (2 mL). Anhydrous Na2SO4 (5.0 g) was added and the solution was stirred at rt for 30 min. The solution was filtered and the solvent was evaporated. The residue was dissolved in EtOAc and washed with saturated aqueous NaHCO3 solution, brine and dried over anhydrous MgSO4. Yield: 95 mg (93%). 1H NMR (400 MHz, CHLOROFORM-D): δ 1.41-1.51 (m, 2H), 1.54 (s, 9H), 1.57-1.67 (m, 2H), 1.68-1.76 (m, 3H), 2.07-2.17 (m, 3H), 2.87 (s, 3H), 4.15 (d, J=7.42 Hz, 2H), 6.61 (dd, J=8.59, 2.34 Hz, 1H), 7.01 (d, J=1.95 Hz, 1H), 7.09 (d, J=8.59 Hz, 1H).

Workup

  1. stirringthe solution was stirred at rt overnight
  2. customThe reaction was quenched at 0° C. by the addition of MeOH (1 mL) and water (2 mL)
  3. additionAnhydrous Na2SO4 (5.0 g) was added
  4. stirringthe solution was stirred at rt for 30 min
  5. filtrationThe solution was filtered
  6. customthe solvent was evaporated
  7. dissolutionThe residue was dissolved in EtOAc
  8. washwashed with saturated aqueous NaHCO3 solution, brine
  9. dry with materialdried over anhydrous MgSO4

Sources & evidence

ORD record
ord-fb9c2c631c4b47649f84dd2423ba4ac7
Source dataset
uspto-grants-2014_01
Patent number
US08633235B2

Reaction notes

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