2-{[(3,5-bis-trifluoromethyl-benzyl)(2-methyl-2H-tetrazol-5-yl)amino]-methyl}-4-trifluoromethyl-benzaldehyde → (2-{[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-cyclohexyl-methanol

HRID 2075018Notes

Reaction equation

HRID 2075018 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:16]=1[CH:17]=[O:18])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[CH:36]1([Mg]Br)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1>C1COCC1>[F:33][C:30]([F:31])([F:32])[C:28]1[CH:27]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:34])[F:35])[CH:29]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:16]=1[CH:17]([CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1)[OH:18])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1

Participants

4

Reactant 2

HCID 589665242-{[(3,5-bis-trifluoromethyl-benzyl)(2-methyl-2H-tetrazol-5-yl)amino]-methyl}-4-trifluoromethyl-benzaldehydeHCID 178419651HCID 178419651, compound

Product 1

HCID 58968665(2-{[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-cyclohexyl-methanolYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-benzaldehyde (244 mg, 0.48 mmoles) in THF (3 mL) at 0° C. was added cyclohexylmagnesium bromide (18% solution in THF, 0.6 mL, 0.57 mmoles) and the reaction was allow to warm to room temperature and stirred overnight. The reaction mixture was quenched with aqueous NH4Cl and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified over 25+S Biotage silica column (eluted with 0-30% ethyl acetate in hexane) to yield 110 mg (39%) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 1.0 (m, 6H) 1.6 (m, 3H) 1.8 (m, 1H) 1.9 (d, J=12.4 Hz, 1H) 2.2 (s, 1H) 4.2 (s, 3H) 4.6 (d, J=7.5 Hz, 1H) 4.8 (m, 4H) 7.3 (s, 1H) 7.5 (m, 2H) 7.6 (s, 2H) 7.8 (s, 1H)). MS (ES+) Calc: 595.2, Found: 596.4 (M+1).

Workup

  1. customThe reaction mixture was quenched with aqueous NH4Cl
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified over 25+S Biotage silica column (eluted with 0-30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-3bf6a98cf57f4d8bba6acd7fda8dfdc0
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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