Hydrochloric Acid → alpha,alpha-dimethyl-N-[4-oxo-1-phenylcyclohexyl]-3,5-bis(trifluoromethyl)benzeneacetamide

HRID 2213062Notes

Reaction equation

HRID 2213062 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][C:8]([CH3:26])([C:12]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]([C:22]([F:25])([F:24])[F:23])[CH:13]=1)[C:9](O)=[O:10].Cl.[O:28]=[C:29]1[CH2:34][CH2:33][C:32]([NH2:41])([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:31][CH2:30]1.N1C=CC=CC=1.Cl>CN(C)C=O.ClCCl>[CH3:7][C:8]([CH3:26])([C:12]1[CH:17]=[C:16]([C:18]([F:19])([F:21])[F:20])[CH:15]=[C:14]([C:22]([F:24])([F:25])[F:23])[CH:13]=1)[C:9]([NH:41][C:32]1([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:31][CH2:30][C:29](=[O:28])[CH2:34][CH2:33]1)=[O:10]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 65578Oxalyl chlorideHCID 98359482-(3,5-Bis(trifluoromethyl)phenyl)-2-methylpropanoic acidHCID 219552264-Oxo-1-phenylcyclohexylamine hydrochloride

Product 1

HCID 21955373alpha,alpha-dimethyl-N-[4-oxo-1-phenylcyclohexyl]-3,5-bis(trifluoromethyl)benzeneacetamideYield 41.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (5.8 mL, 66.6 mmol) was added slowly to a solution of α,α-dimethyl-3,5-bis(trifluoromethyl)benzeneacetic acid (Description 6, 10 g, 33.3 mmol) and dimethylformamide (1 drop) in dichloromethane (100 mL) and. the mixture was stirred at room temperature for 24 hours. The solvent was evaporated under reduced pressure and the residue was dissolved in dichloromethane (20 mL) and added slowly to a solution of 4-oxo-1-phenylcyclohexylamine hydrochloride (Description 18, 8.2 g, 43.4 mmol) and pyridine (5.7 mL, 66.3 mmol) in dichloromethane (100 mL). The mixture was stirred at room temperature for 24 hours, then hydrochloric acid (2M, 100 mL) was added. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatograph on silica gel, eluting with isohexane:EtOAc (75:25), to give the title compound as a colorless solid (6.5 g, 41%). 1H NMR (400 MHz, CDCl3) δ 7.83 (1H, s), 7.77 (2H, s), 7.35–7.26 (5H, m), 5.44 (1H, s), 2.70–2.66 (2H, m), 2.40–2.30 (6H, m), and 1.62 (6H, s).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in dichloromethane (20 mL)
  3. stirringThe mixture was stirred at room temperature for 24 hours
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with dichloromethane
  6. dry with materialThe combined organic fractions were dried (MgSO4)
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by flash column chromatograph on silica gel
  9. washeluting with isohexane:EtOAc (75:25)

Sources & evidence

ORD record
ord-8f42c99be31342f9ac3d474b64083a6b
Source dataset
uspto-grants-2006_09
Patent number
US07105507B2

Reaction notes

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