Ether hydrochloride → 2-tert-Butyl-1-(cyclohexylmethyl)-N-methyl-1H-benzimidazol-5-amine

HRID 1783892Notes

Reaction equation

HRID 1783892 reaction equation
CO[C:3](=O)[NH:4][C:5]1[CH:24]=[CH:23][C:8]2[N:9]([CH2:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])=[N:11][C:7]=2[CH:6]=1.Cl.CCOCC.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[C:12]([C:10]1[N:9]([CH2:16][CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C:8]2[CH:23]=[CH:24][C:5]([NH:4][CH3:3])=[CH:6][C:7]=2[N:11]=1)([CH3:15])([CH3:13])[CH3:14]

Participants

5

Reactant 3

HCID 10953452Ether hydrochlorideHCID 11588208Methyl [2-tert-butyl-1-(cyclohexylmethyl)-1H-benzimidazol-5-yl]carbamateHCID 21226445Aluminium lithium hydride

Product 1

HCID 116307962-tert-Butyl-1-(cyclohexylmethyl)-N-methyl-1H-benzimidazol-5-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Methyl[2-tert-butyl-1-(cyclohexylmethyl)-1H-benzimidazol-5-yl]carbamate (650 mg, 1.89 mmol) was dissolved in 20 mL of THF at 0° C. under nitrogen. 1M HCl/ether (2.65 mL, 2.65 mmol) was added dropwise and the solution stirred at 0° C. for 15 min. LiAlH4 (360 mg, 9.45 mmol) was then slowly added and the solution stirred at RT overnight. The reaction mixture was quenched at 0° C. by addition of MeOH (5 mL) followed by water (10 mL). The solution was diluted with EtOAc and washed with saturated NaHCO3 aqueous solution, brine and dried over anhydrous MgSO4. The solvent was evaporated and the product was used directly in the next step without further purification. Yield: 544 mg (96%). 1H NMR (400 MHz, CHLOROFORM-D) δ 1.08 (m, 2H), 1.17 (m, 3H), 1.53 (s, 9H), 1.64 (s, 2H), 1.67 (s, 2H), 1.72 (m, 2H), 2.02 (m, 1H), 2.86 (s, 3H), 4.06 (d, J=7.42 Hz, 2H), 6.60 (dd, J=8.69, 2.25 Hz, 1H), 6.99 (d, J=2.15 Hz, 1H), 7.12 (d, J=8.59 Hz, 1H).

Workup

  1. stirringthe solution stirred at RT overnight
  2. customThe reaction mixture was quenched at 0° C. by addition of MeOH (5 mL)
  3. additionThe solution was diluted with EtOAc
  4. washwashed with saturated NaHCO3 aqueous solution, brine
  5. dry with materialdried over anhydrous MgSO4
  6. customThe solvent was evaporated
  7. customthe product was used directly in the next step without further purification

Sources & evidence

ORD record
ord-d46b3c62044847c4bcb3f8670203ab74
Source dataset
uspto-grants-2009_03
Patent number
US07501447B2

Reaction notes

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