Boron trifluoride → rel-(3R,4S)-4-(4-Fluorophenyl)tetrahydro-3-furanol

Temperature

-90 °C

1.6M BuLi/hexane (399 mL, 0.64 mol, 1.10 eq) was added to a solution of 1-bromo-4-fluorobenzene (70 mL, 0.64 mol, 1.10 eq) in absolute THF (400 mL) in a stream of argon at −90° C. for 1 h. The mixture was stirred at −90° C. for 30 min, cooled to −100° C., and 3,6-dioxabicyclo[3.1.0]hexane (50 g, 0.58 mol, 1 eq) was added. The mixture was stirred at −100° C. for 15 min, and borontrifluoride diethyletherate (81 mL, 0.64 mol, 1.10 eq) was added at the same temperature for 1 h so that the temperature was no higher than −80° C. The reaction mixture was heated to 0° C. for 3 h and diluted with hexane (300 mL) and water (300 mL). 10N sodium hydroxide (50 mL) was added, and the layers were separated. The aqueous layer was extracted with ether. The organic layer was washed with the saturated sodium chloride solution, dried over sodium sulfate, and evaporated. The mixture was subjected to chromatography on silica (1 L, carbon tetrachloride→25, 50, 75, 100% chloroform) to give title compound as a yellow oil (42 g, 0.23 mol, 39.7%).

1. temperaturecooled to −100° C.
2. stirringThe mixture was stirred at −100° C. for 15 min
3. customwas no higher than −80° C
4. temperatureThe reaction mixture was heated to 0° C. for 3 h
5. customthe layers were separated
6. extractionThe aqueous layer was extracted with ether
7. washThe organic layer was washed with the saturated sodium chloride solution
8. dry with materialdried over sodium sulfate
9. customevaporated

ORD record

ord-ff036b0b36e04294bb2a68a523e5e692

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08357711B2