Aluminium lithium hydride → [2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazol-4-yl]methanol

HRID 539198Notes

Reaction equation

HRID 539198 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[C:9]=2[CH3:18])[C:5]2[CH:19]=[C:20]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[CH:21]=[C:22]([C:23](OC)=[O:24])[C:4]=2[N:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>O1CCCC1>[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:16])([F:15])[F:17])[C:9]=2[CH3:18])[C:5]2[CH:19]=[C:20]([N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[CH:21]=[C:22]([CH2:23][OH:24])[C:4]=2[N:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 56959828methyl 2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylate

Product 1

HCID 56960404[2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazol-4-yl]methanolYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of methyl 2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylate, prepared as described in Example 30 (0.37 g, 0.827 mmol) in Tetrahydrofuran (THF) (10 mL) was cooled to 0° C. LiAlH4 (0.038 g, 1 mmol) in THF (3 mL) was added in and the reaction mixture was stirred at 0° C. for 30 min. The reaction mixture was quenched with water (0.04 mL), NaOH (15%, 0.04 mL) then water (0.12 mL). Anhydrous MgSO4 was added and the reaction mixture was filtered through celite and washed with EtOAc. Evaporation of the solvent gave the crude product. The crude product was purified on a silica column (1˜4% MeOH/DCM) to give the solid (0.32 g, 88%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.35 (s, 3H), 2.56 (s, 3H), 2.99-3.07 (m, 4H), 3.67-3.76 (m, 4H), 4.87 (d, J=5.81 Hz, 2H), 5.11 (t, J=5.68 Hz, 1H), 5.51 (s, 2H), 6.30 (d, J=7.83 Hz, 1H), 6.81 (d, J=2.27 Hz, 1H), 6.97 (d, J=2.02 Hz, 1H), 7.24 (t, J=7.83 Hz, 1H), 7.60 (d, 1H). MS (ES+) m/z 420.1 [M+H]+.

Workup

  1. customThe reaction mixture was quenched with water (0.04 mL), NaOH (15%, 0.04 mL)
  2. additionAnhydrous MgSO4 was added
  3. filtrationthe reaction mixture was filtered through celite
  4. washwashed with EtOAc
  5. customEvaporation of the solvent
  6. customgave the crude product
  7. customThe crude product was purified on a silica column (1˜4% MeOH/DCM)

Sources & evidence

ORD record
ord-a67f1e4558e54f81ae0acc63996ee888
Source dataset
uspto-grants-2014_10
Patent number
US08865912B2

Reaction notes

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