Pyridine → (RS)-alpha-(3-Butenyl)-N-(4-oxo-1-phenylcyclohexyl)-3,5-bis(trifluoromethyl)-benzeneacetamide

HRID 852678Notes

Reaction equation

HRID 852678 reaction equation
C(Cl)(=O)C(Cl)=O.[CH2:7]([CH:11]([C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([C:25]([F:28])([F:27])[F:26])[CH:16]=1)[C:12]([OH:14])=O)[CH2:8][CH:9]=[CH2:10].Cl.[O:30]=[C:31]1[CH2:36][CH2:35][C:34]([NH2:43])([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:33][CH2:32]1.N1C=CC=CC=1>ClCCl.CN(C)C=O>[CH2:7]([CH:11]([C:15]1[CH:16]=[C:17]([C:25]([F:27])([F:28])[F:26])[CH:18]=[C:19]([C:21]([F:24])([F:22])[F:23])[CH:20]=1)[C:12]([NH:43][C:34]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:33][CH2:32][C:31](=[O:30])[CH2:36][CH2:35]1)=[O:14])[CH2:8][CH:9]=[CH2:10]

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 219552264-Oxo-1-phenylcyclohexylamine hydrochlorideHCID 86594176(RS)-alpha-(3-butenyl)-3,5-bis(trifluoromethyl)benzeneacetic acid

Product 1

HCID 86594175(RS)-alpha-(3-Butenyl)-N-(4-oxo-1-phenylcyclohexyl)-3,5-bis(trifluoromethyl)-benzeneacetamideYield 52%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (4.22 mL, 48.4 mmol) was added to a solution of (RS)-α-(3-butenyl)-3,5-bis(trifluoromethyl)benzeneacetic acid (Description 8, 24.2 mmol) and dimethylformamide (0.1 mL) in dichloromethane (80 mL) and the mixture was stirred at room temperature for 3 hours. The solvent was evaporated under reduced pressure and toluene was added and evaporated under reduced pressure. The residue was dissolved in dichloromethane (50 mL) and added to a stirred, cooled (0° C.) solution of 4-oxo-1-phenylcyclohexylamine hydrochloride (Description 3, 4.58 g, 24.2 mmol) in dichloromethane (150 mL). Pyridine (4.1 mL, 50.8 mmol) was added and the mixture was stirred at room temperature overnight. The mixture was washed with hydrochloric acid (1M, 2×200 mL), saturated aqueous sodium hydrogen carbonate (2×200 mL) and brine (200 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was triturated with isohexane/diethylether (7:1) and the solid was collected and dried in vacuo. The solid was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (2:1), to give the title compound (6.22 g, 52%). 1H NMR (400 MHz, CDCl3) δ 7.80 (1H, s), 7.73 (2H, s), 7.31-7.25 (5H, m), 5.80-5.70 (2H, m), 5.05-4.97 (2H, m), 3.52-3.47 (1H, m), 2.86-2.80 (1H, m), 2.65-2.57 (1H, m), 2.50-2.31 (6H, m), 2.27-2.18 (1H, m), 2.09-1.95 (2H, m), and 1.81-1.72 (1H, m).

Workup

  1. customThe solvent was evaporated under reduced pressure and toluene
  2. additionwas added
  3. customevaporated under reduced pressure
  4. dissolutionThe residue was dissolved in dichloromethane (50 mL)
  5. additionadded to a stirred
  6. stirringthe mixture was stirred at room temperature overnight
  7. washThe mixture was washed with hydrochloric acid (1M, 2×200 mL), saturated aqueous sodium hydrogen carbonate (2×200 mL) and brine (200 mL)
  8. dry with materialdried (MgSO4)
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was triturated with isohexane/diethylether (7:1)
  11. customthe solid was collected
  12. customdried in vacuo
  13. customThe solid was purified by flash column chromatography on silica gel
  14. washeluting with isohexane/EtOAc (2:1)

Sources & evidence

ORD record
ord-78e77587c4e34af3b10330fa76d6580d
Source dataset
uspto-grants-2007_08
Patent number
US07253205B2

Reaction notes

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