tert-Butanol → 3-(4-Bromo-3-fluorophenyl)-5-(hydroxymethyl)-1,3-oxazolidin-2-one

Temperature

-30 °C

Butyl lithium (2.3M in n-hexanes, 118.3 ml, 0.272 mol, 1.06 eq) was added at −30° C. to anhydrous tert-butanol (25.0 g, 0.53 mol, 2.07 eq) in anhydrous THF (170 ml), under nitrogen. The mixture was stirred for 30 min at −30° C., and was then allowed to warm slowly to 0° C. After 30 min at 0° C., the (4-bromo-3-fluoro-phenyl)-carbamic acid benzyl ester (83 g, 0.256 mol, 1 eq) was added portionwise, keeping the temperature cold, and the mixture was stirred for an additional 30 min at 0° C. To this ice cold mixture, R(−)-glycidyl butyrate (39.7 ml, 0.288 mol, 1.12 eq) were added and the mixture allowed to come gradually to room temperature. The mixture was extracted with saturated sodium chloride solution and the organic phase was dried over MgSO4, filtrated and evaporated. The product was obtained after recrystallisation of the crude product with ethyl acetate, to give (64.1 g, 86.4%).

1. temperatureto warm slowly to 0° C
2. waitAfter 30 min at 0° C.
3. stirringthe mixture was stirred for an additional 30 min at 0° C
4. customto come gradually to room temperature
5. extractionThe mixture was extracted with saturated sodium chloride solution
6. dry with materialthe organic phase was dried over MgSO4
7. filtrationfiltrated
8. customevaporated
9. customThe product was obtained
10. customafter recrystallisation of the crude product with ethyl acetate
11. customto give (64.1 g, 86.4%)

ORD record

ord-c8d09b8ec1c340c69c2cdf5822c76748

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158797B2