(2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-cyclohexyl-methanone → 1-(2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)-1-cyclohexylethanol

HRID 2075089Notes

Reaction equation

HRID 2075089 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[C:25]([CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)=[O:26])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[CH3:42][Mg]Br>O1CCCC1>[F:41][C:2]([F:1])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:37])([F:38])[F:39])[CH:35]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[C:25]([CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)([OH:26])[CH3:42])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1

Participants

4

Reactant 2

HCID 58968633(2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-cyclohexyl-methanoneHCID 178418573HCID 178418573, compound

Product 1

HCID 589686081-(2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)-1-cyclohexylethanolYield 108%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-cyclohexyl-methanone (143 mg; 0.241 mmol) in tetrahydrofuran (2.5 mL) at 0° C. was added 3.0M methylmagnesium bromide in tetrahydrofuran (0.25 mL; 0.75 mmol). After 15 minutes, the bath was removed and reaction was stirred at room temperature for 3 hours. The reaction was quenched with 2 drops of water. The reaction was diluted with ethyl acetate and dried over sodium sulfate and concentrated under reduced pressure. The residue was purified over 12 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 10-50% ethyl acetate in heptane) to give 158 mg (108% yield) of a colorless oil. MS (ES+): Calc: 609.5, Found: 610.4 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm 7.77 (s, 1H), 7.74 (s, 1H) 7.42 (m, 2H), 7.34 (d, J=8.30 Hz, 1H), 5.46 (d, J=16.18 Hz, 1H), 4.93 (d, J=16.60 Hz, 1H), 4.82 (q, J=16.18 Hz, 2H), 4.18 (s, 3H), 1.78-1.6 (m, 6H), 1.58 (s, 3H), 1.40 (m, 1H), 1.13-0.94 (m, 4H).

Workup

  1. customthe bath was removed
  2. customreaction
  3. customThe reaction was quenched with 2 drops of water
  4. additionThe reaction was diluted with ethyl acetate
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified over 12 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 10-50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-47ae821cb37b4bbc90f7139af0634823
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

Loading…