Ether hydrochloride → 2-tert-Butyl-N-methyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-amine

HRID 472944Notes

Reaction equation

HRID 472944 reaction equation
[C:1]([C:5]1[N:9]([CH2:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:8]2[CH:17]=[CH:18][C:19]([NH:21][C:22](=O)OC)=[CH:20][C:7]=2[N:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.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][O:14][CH2:13][CH2:12]2)[C:8]2[CH:17]=[CH:18][C:19]([NH:21][CH3:22])=[CH:20][C:7]=2[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 10953452Ether hydrochlorideHCID 21226445Aluminium lithium hydrideHCID 57723208Methyl [2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]carbamate

Product 1

HCID 574410762-tert-Butyl-N-methyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Methyl [2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]carbamate (1.80 g, 5.21 mmol) was dissolved in 75 mL of THF at 0° C. 1M HCl/ether (7.3 mL, 7.29 mmol) was added dropwise and the solution was stirred at 0° C. for 15 min. LiAlH4 (988 mg, 26.1 mmol) was added slowly and the solution was stirred at rt overnight. The reaction was quenched at 0° C. by the addition of MeOH (5 mL) followed by water (10 mL) and the solution was left to stir at rt for 30 min. Anhydrous Na2SO4 (10 g) was added and the solution was stirred at rt for another 30 min. The solution was filtered and the solvent was evaporated. The residue was dissolved in EtOAc and washed with aqueous NaHCO3 solution, brine and dried over anhydrous MgSO4. The solvent was evaporated. Yield: 1.54 g (98%). 1H NMR (400 MHz, CHLOROFORM-D): δ 1.49-1.53 (m, 4H), 1.53-1.57 (m, 9H), 2.22-2.32 (m, 1H), 2.87 (s, 3H), 3.26-3.35 (m, 2H), 3.95 (t, J=3.03 Hz, 1H), 3.97-4.00 (m, 1H), 4.13 (d, J=7.42 Hz, 2H), 6.61 (dd, J=8.59, 2.15 Hz, 1H), 6.99 (d, J=1.95 Hz, 1H), 7.11 (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 (5 mL)
  3. waitthe solution was left
  4. stirringto stir at rt for 30 min
  5. additionAnhydrous Na2SO4 (10 g) was added
  6. stirringthe solution was stirred at rt for another 30 min
  7. filtrationThe solution was filtered
  8. customthe solvent was evaporated
  9. dissolutionThe residue was dissolved in EtOAc
  10. washwashed with aqueous NaHCO3 solution, brine
  11. dry with materialdried over anhydrous MgSO4
  12. customThe solvent was evaporated

Sources & evidence

ORD record
ord-729bb5b5149547379a3a81b3674c50d4
Source dataset
uspto-grants-2014_01
Patent number
US08633235B2

Reaction notes

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