Water → 3-phenyl-2H-pyran

Dimethylsulfoxide (10 mL) was added to sodium hydride (60% dispersion in mineral oil, 385 mg, 9.6 mmol) and the mixture was stirred at room temperature for 30 minutes. Tetrahydrofuran (20 mL) was added and the mixture was cooled to −10° C. Trimethylsulfonium iodide (2.13 g, 10.4 mmol) in dimethylsulfoxide (10 mL) was added and the mixture was stirred at 0° C. for 10 minutes. (2R,3R,4R)-2-{(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy}tetrahydro-3-phenyl-2H-pyran-4-carboxaldehyde (WO 00/56727A1; 3.58 g, 8.0 mmol) in tetrahydrofuran (10 mL) was added and the mixture was stirred at 0° C. for 30 minutes, then at room temperature for 30 minutes. Water (100 mL) was added and the mixture was extracted with ethyl acetate (3×100 mL). The combined organic fractions were washed with water (4×100 mL) and brine (100 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with hexane/EtOAc (85:15 increasing to 80:20), to give (2R,3R,4R)-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}tetrahydro-4-[(2R or S)-oxiranyl]-3-phenyl-2H-pyran (Isomer A; single diastereoisomer; epoxide stereochemistry unassigned) as a colorless oil (1.37 g, 37%); 1H NMR (500 MHz, CDCl3): δ 7.67 (1H, s), 7.23 (5H, m), 7.01 (2H, m), 4.97 (1H, q, J 6.6 Hz), 4.28 (1H, d, J 8.4 Hz), 4.16 (1H, br d, J 11 Hz), 3.53 (1H, br t, J 11 Hz), 2.65 (1H, dd, J 8.4 Hz), 2.60 (1H, m), 2.34 (1H, t, J 4.5 Hz), 1.95 (1H, dd, J 4.5, 2.7 Hz), 1.84 (1H, br d, J 11 Hz), 1.68 (1H, m), 1.57 (1H, m), 1.37 (3H, d, J 6.6 Hz); and

1. temperaturethe mixture was cooled to −10° C
2. stirringthe mixture was stirred at 0° C. for 10 minutes
3. stirringthe mixture was stirred at 0° C. for 30 minutes
4. waitat room temperature for 30 minutes
5. extractionthe mixture was extracted with ethyl acetate (3×100 mL)
6. washThe combined organic fractions were washed with water (4×100 mL) and brine (100 mL)
7. dry with materialdried (MgSO4)
8. customthe solvent was evaporated under reduced pressure
9. customThe residue was purified by column chromatography on silica gel
10. washeluting with hexane/EtOAc (85:15 increasing to 80:20)

ORD record

ord-6212af817f524f2faf674e893145977d

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07393858B2