Water → HCID 58754968, compound

Temperature

-65 °C

To a commercially obtained tetrahydrofuran solution of lithium bis(trimethyl-silyl)amide (1.0 M, 21.0 mL), stirred under a nitrogen atmosphere and cooled to an internal temperature of −65° C., was added dropwise over 30 minutes a solution of methyl 2,4,6-trifluorobenzeneacetate (i.e. the product of Step A) (2.04 g, 10.0 mmol) dissolved in dry tetrahydrofuran (10 mL). The reaction mixture was stirred for an additional 30 minutes, and then while maintaining the −65° C. temperature, a solution of freshly distilled acetyl chloride (0.80 mL, 11 mmol) in dry tetrahydrofuran (3 mL) was added dropwise. The reaction mixture was allowed to warm slowly to ambient temperature, and then water (30 mL) was added. The resultant mixture was extracted with ethyl acetate (60 mL). The aqueous phase was acidified with 1 N hydrochloric acid and extracted with ethyl acetate (60 mL). Only the first extract was retained, because thin layer chromatographic analysis showed the second extract to contain apparent polar impurities besides additional desired product. The initial organic phase was further washed with 1 N hydrochloric acid, water and brine, dried over MgSO4, and concentrated to provide the title product as a clear oil (1.86 g).

1. temperaturewhile maintaining the −65° C. temperature
2. temperatureto warm slowly to ambient temperature
3. extractionThe resultant mixture was extracted with ethyl acetate (60 mL)
4. extractionextracted with ethyl acetate (60 mL)
5. extractionOnly the first extract
6. extractionextract
7. washThe initial organic phase was further washed with 1 N hydrochloric acid, water and brine
8. dry with materialdried over MgSO4
9. concentrationconcentrated

ORD record

ord-f78416bab7e1417591e1a884437f1e78

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062005B2