Sodium Fluoride → HCID 58046435, compound

Temperature

0 °C

A solution of (1R)-1-phenylethanamine (30, 72 mL, 0.57 mol) in dichloromethane (200 mL) was cooled to 0° C. and treated with trimethylaluminum (260 mL, 0.52 mol) and the resulting solution was stirred for 1 hour at 0° C. To this solution was added a solution of 2,2-difluoro-7-oxabicyclo[4.1.0]heptane (66 g, 0.49 mol) in dichloromethane (200 mL) and the resulting mixture stirred at 0° C. for 3 hours. The reaction was then warmed to ambient temperature for 16 hours. The reaction was cooled to 0° C., treated with 103 g of sodium fluoride and then quenched with water (90 mL, slow addition). The reaction was warmed to ambient temperature, the solids filtered and the solution evaporated in vacuo. Purification by flash chromatography (50-100% ethyl acetate in hexanes) gave 36.3 g (29%) of (1S,6R)-2,2-difluoro-6-{[(1R)-1-phenylethyl]amino}cyclohexanol 31 (plus 32 g of 1R,6S diastereomer) as a white solid: 1H NMR (500 MHz, CDCl3) δ 7.32 (5H, s), 3.90 (1H, q, J=6.6 Hz,), 3.39 (1H, ddd, J=19.8, 9.8, 4.2 Hz), 2.70 (1H, m), 2.11 (1H, m), 1.80 (1H, m), 1.62 (2H, m), 1.43 (1H, m), 1.36 (3H, d, J=6.6 Hz), 0.96 (1H, m).

1. stirringthe resulting mixture stirred at 0° C. for 3 hours
2. temperatureThe reaction was then warmed to ambient temperature for 16 hours
3. temperatureThe reaction was cooled to 0° C.
4. customquenched with water (90 mL, slow addition)
5. temperatureThe reaction was warmed to ambient temperature
6. filtrationthe solids filtered
7. customthe solution evaporated in vacuo
8. customPurification by flash chromatography (50-100% ethyl acetate in hexanes)

ORD record

ord-1e0e9734b94c441cad19997b385a9a52

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08461162B2