Water → (RS)-alpha-Methyl-N-(4-methylene-1-phenylcyclohexyl)-3,5-bis(trifluoromethyl) benzeneacetamide

HRID 2213064Notes

Reaction equation

HRID 2213064 reaction equation
[CH2:1]([Li])CCC.[CH3:6][CH:7]([C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[C:26]([C:34]([F:37])([F:36])[F:35])[CH:25]=1)[C:8]([NH:10][C:11]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]1)=[O:9].O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[CH3:6][CH:7]([C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[C:26]([C:34]([F:36])([F:35])[F:37])[CH:25]=1)[C:8]([NH:10][C:11]1([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:12][CH2:13][C:14](=[CH2:1])[CH2:15][CH2:16]1)=[O:9]

Participants

6

Reactant 3

HCID 962WaterHCID 21955177N-[1-Phenyl-4-oxocyclohexyl]-2-[3,5-bis(trifluoromethyl)phenyl]propionamideHCID 178418339Butyllithium

Product 1

HCID 21955125(RS)-alpha-Methyl-N-(4-methylene-1-phenylcyclohexyl)-3,5-bis(trifluoromethyl) benzeneacetamideYield 91%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

n-Butyllithium (1.6 Mol solution in hexanes, 10.3 mL) was added slowly to a stirred, cooled (0° C.) suspension of methyl triphenylphosphonium bromide (5.86 g, 16.4 mmol) in tetrahydrofuran (60 mL) and the mixture was stirred at room temperature for 3 hours. The mixture was cooled to 0° C. and (RS)-α-methyl-N-(4-oxo-1-phenylcyclohexyl)-3,5-bis(trifluoromethyl)benzeneacetamide (Example 3, 3.0 g, 6.56 mmol) in tetrahydrofuran (20 mL) was added. The mixture was stirred at room temperature for 1 hour, then under reflux for 3 hours. The mixture was cooled, poured into water and extracted with ethyl acetate. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by chromatography on a short column of silica gel, eluting with dichloromethane, to give the title compound as a colorless solid (2.27 g, 91%). 1H NMR (400 MHz, CDCl3) δ 7.80 (1H, s), 7.75 (2H, s), 7.26–7.20 (5H, m), 5.59 (1H, s), 4.68 (2H, m), 3.70 (1H, d, J 7.1 Hz), 2.53–2.45 (1H, m), 2.38–2.31 (1H, m), 2.29–2.04 (4H, m), 2.00–1.85 (2H, m), and 1.52 (3H, d, J, 7.1 Hz).

Workup

  1. temperaturecooled
  2. temperatureThe mixture was cooled to 0° C.
  3. stirringThe mixture was stirred at room temperature for 1 hour
  4. temperatureunder reflux for 3 hours
  5. temperatureThe mixture was cooled
  6. extractionextracted with ethyl acetate
  7. dry with materialThe combined organic fractions were dried (MgSO4)
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by chromatography on a short column of silica gel
  10. washeluting with dichloromethane

Sources & evidence

ORD record
ord-8e006261a1a6410f865d5b263ed24c72
Source dataset
uspto-grants-2006_09
Patent number
US07105507B2

Reaction notes

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