Hydrochloric Acid → 4,4-Difluoro-1-(hydroxymethyl)cyclohexan-1-ol

Temperature

50 °C

To the solution from EXAMPLE 302D was added water (75 mL), then N-methylmorpholine-N-oxide (6.4 mL, 50% solution in water) and OsO4 (14.2 g, 2.5 wt % solution in tert-butanol) were added, and the reaction was stirred for 96 hours at 50° C. The solution was cooled to room temperature, treated with saturated aqueous Na2S2O3 solution (100 mL) for 30 minutes, and then acidified with concentrated aqueous HCl. The solution was then extracted three times with ethyl acetate, and the organic layers were combined, washed with 1M HCl, and brine, and concentrated. The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes, and then 5% methanol in ethyl acetate to give the product.

1. temperatureThe solution was cooled to room temperature
2. extractionThe solution was then extracted three times with ethyl acetate
3. washwashed with 1M HCl, and brine
4. concentrationconcentrated
5. customThe crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes
6. custom5% methanol in ethyl acetate to give the product

ORD record

ord-f70a0dcead804fa19b2dbfdc7fdd56bd

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09034875B2