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

Bis(2-oxo-3-oxazolidinyl)phosphinic chloride (672 mg, 2.64 mmol) was added to a solution of (S)-α-methyl-3,5-bis(trifluoromethyl)benzeneacetic acid (Description 40, 500 mg, 1.76 mmol) and pyridine (284 μL, 3.52 mmol) in dichloromethane (15 mL) and the mixture was stirred at room temperature for 5 minutes. 4-Oxo-1-phenylcyclohexylamine hydrochloride (Description 18, 500 mg, 2.64 mmol) was added and the mixture was stirred at room temperature for 48 hours. The mixture was diluted with dichloromethane and washed with saturated aqueous sodium carbonate. The organic layer was dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane:EtOAc (65:35). The residue was crystallised twice from propan-2-ol/water (50:50, 20 mL) and the solid was collected and dried in vacuo to give the title compound as a colorless solid (200 mg, 37%). 1H NMR (400 MHz, CDCl3) δ 7.80 (1H, s), 7.72 (2H, s), 7.29 (5H m), 5.71 (1H, s), 3.70 (1H, q, J 7.0 Hz), 2.81 (1H, m), 2.64 (1H, m), 2.47–2.04 (5H, m), 1.60 (1H, m), and 1.52 (3H, d, J 7.0 Hz). e.e. [Determined by chiral HPLC (Chiralcel OD-H 250×4.6 mm i.d.; isohexane/EtOH (96:4); 1 mL/min; 210 nm]>99%.

1. stirringthe mixture was stirred at room temperature for 48 hours
2. washwashed with saturated aqueous sodium carbonate
3. dry with materialThe organic layer was dried (MgSO4)
4. customthe solvent was evaporated under reduced pressure
5. customThe residue was purified by flash column chromatography on silica gel
6. washeluting with isohexane:EtOAc (65:35)
7. customThe residue was crystallised twice from propan-2-ol/water (50:50, 20 mL)
8. customthe solid was collected
9. customdried in vacuo

ORD-Eintrag

ord-beea6d8fa08e465fb697ce07e82c6013

Quelldatensatz

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07105507B2