Water → HCID 58968625, compound

HRID 2075045Notes

Reaction equation

HRID 2075045 reaction equation
[F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([CH:35]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:37]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[C:18]([CH3:25])=[CH:17][C:16]=1[C:26]([CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)([OH:28])[CH3:27])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[H-].[Na+].[CH3:46]I.O>C1COCC1>[CH:29]1([C:26]([C:16]2[CH:17]=[C:18]([CH3:25])[C:19]([C:21]([F:24])([F:23])[F:22])=[CH:20][C:15]=2[CH2:14][N:7]([CH2:6][C:5]2[CH:35]=[C:36]([C:38]([F:39])([F:40])[F:41])[CH:37]=[C:3]([C:2]([F:1])([F:42])[F:43])[CH:4]=2)[C:8]2[N:9]=[N:10][N:11]([CH3:13])[N:12]=2)([O:28][CH3:46])[CH3:27])[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58968605HCID 58968605, compound

Product 1

HCID 58968625HCID 58968625, compoundYield 95.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-5-methyl-4-(trifluoromethyl)phenyl)-1-cyclohexylethanol (18 mg, 0.028 mmol) in THF (3 mL) was added sodium hydride (60% dispersion in mineral oil, 8 mg, 0.202 mmol) at room temperature. After stirring for 5 minutes methyl iodide (12.2 mg, 0.086 mmol) was added and the solution was stirred at room temperature for 18 hours. Water (5 mL) was added and the mixture was extracted with ethyl acetate (3×20 mL). The organics were combined, dried with anhydrous sodium sulfate, filtered and concentrated to give an oil (17 mg). This material was purified by flash chromatography on a 4 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 10% ethyl acetate in heptane) to yield the title compound (11 mg, 59%). 1H NMR (400 MHz, CDCl3) δ7.75 (s, 1H) 7.70 (s, 2H) 7.39 (s, 1H) 7.01 (s, 1H) 5.19 (d, J=17.42 Hz, 1H) 5.0 (d, J=17.42 Hz, 1H) 4.74 (q, J=16.72 Hz, J=16.18 Hz, 2H) 4.17 (s, 3H) 3.0 (s, 3H) 2.42 (s, 3H) 1.99 (d, J=12.40 Hz, 1H) 1.72 (m, 2H) 1.58 (s, 3H) 0.99 (m, 8H). MS calc. 637.5, found 638.5 (M+H)

Workup

  1. additionwas added
  2. extractionthe mixture was extracted with ethyl acetate (3×20 mL)
  3. dry with materialdried with anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-465678cacbde46a4bd74901d12c9de4f
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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