Tetrafluoroboric acid → HCID 42639483, Verbindung

Temperatur

0 °C

To a solution of 9.09 g (26.9 mmol) of the first eluting isomer diethyl(1S,2S,3R,4S)-3-(4-fluorophenyl)-4-hydroxycyclohexane-1,2-dicarboxylate (step D) and 21.5 g (53.5 mmol) of (1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl-2,2,2-trichloroethanimidoate (step E) in 250 mL of cyclohexane/1,2-chloroethane (3/1) under nitrogen atmosphere at −5° C. was added 0.51 mL (3.58 mmol) of 54% HBF4 in ether. The reaction mixture was stirred at −5° C. to at 0° C. for 2 hr then diluted with ether. The mixture was washed with sat. aq. NaHCO3. The organic layer was dried over drying agent, filtered and the solvent evaporated under vacuum. The residue was purified by flash column chromatography on silica gel eluting with EtOAc/hexanes (1/4) to give 9.2 g of the title compound as an oil. 1H-NMR (CDCl3): δ: δ: 7.70 (1 H, s), 7.20 (2 H, s), 7.00 (2 H, m), 6.85 (2 H, t, J=8.5 Hz), 4.43 (1 H, q, J=6.0 Hz), 4.20-4.10 (2 H, m), 3.80-3.73 (2 H, m), 3.36 (1 H, m), 2.90-2.76 (2 H, m), 2.40 (1 H, m), 2.28 (1 H, m), 1.63-1.55 (2 H, m), 1.33 (3 H, d, J=6.0 Hz), 1.25 (3 H, t, J=7.2 Hz), 0.82 (3 H, t, J=7.2 Hz). Unreacted starting alcohol could be recovered by flushing the column with EtOAc and reused in the above reaction.

1. washThe mixture was washed with sat. aq. NaHCO3
2. customThe organic layer was dried
3. customover drying agent
4. filtrationfiltered
5. customthe solvent evaporated under vacuum
6. customThe residue was purified by flash column chromatography on silica gel eluting with EtOAc/hexanes (1/4)

ORD-Eintrag

ord-e0611fbf4e3545bc8101d4b27bc1b800

Quelldatensatz

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07345083B2