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Methyl iodide → (3,5-Bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amine

HRID 2075019
Notes
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Reaction equation

HRID 2075019 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[CH:25]([CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[OH:26])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[H-].[Na+].[CH3:44]I>C1COCC1>[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[CH:25]([CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[O:26][CH3:44])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58968665(2-{[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-cyclohexyl-methanol

Product 1

HCID 58968680(3,5-Bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amineYield 83.7%

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-phenyl)-cyclohexyl-methanol (35.5 mg, 0.059 mmoles) in THF (0.3 mL) at 0° C. under nitrogen was added sodium hydride (4.8 mg, 0.12 mmoles, 60% dispersion in mineral oil). The reaction was stirred for 30 min., allowing it to warm to room temperature. The reaction mixture was then treated in a dropwise manner with methyl iodide (11 μL, 0.179 mmoles) at 0° C. The ice bath was removed after the addition and the reaction was stirred at room temperature overnight. Solvent was removed in vacuo. The residue was purified using silica gel chromatography over 12+S Biotage silica column (eluted with 0-30% ethyl acetate in hexanes) to yield the title compound (30.1 mg, 83%) as colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.1 (m, 6H) 1.5 (m, 1H) 1.6 (m, 2H) 1.7 (m, 1H) 1.9 (d, J=12.9 Hz, 1H) 3.1 (s, 3H) 4.1 (d, J=7.1 Hz, 1H) 4.2 (s, 3H) 4.7 (d, J=15.8 Hz, 1H) 4.7 (s, 2H) 4.9 (d, J=16.2 Hz, 1H) 7.3 (s, 1H) 7.5 (d, J=7.9 Hz, 1H) 7.6 (d, J=8.3 Hz, 1H) 7.7 (s, 2H) 7.8 (s, 1H). MS (ES+) Calc: 609.2, Found: 610.4 (M+1).

Workup

  1. customThe ice bath was removed
  2. additionafter the addition
  3. stirringthe reaction was stirred at room temperature overnight
  4. customSolvent was removed in vacuo
  5. customThe residue was purified
  6. washover 12+S Biotage silica column (eluted with 0-30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-98dea9d60e464b3fabf9e4c60330052d
Source dataset
uspto-grants-2011_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07919506B2

Reaction notes

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