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 ethyl acetate extract was retained, because thin layer chromatographic analysis showed the second extract to contain apparent polar impurities besides additional desired product. The first ethyl acetate extract was further sequentially washed with 1 N hydrochloric acid, water and brine, dried (MgSO4), and concentrated to provide the title compound 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 ethyl acetate extract
6. extractionextract
7. extractionThe first ethyl acetate extract
8. washwas further sequentially washed with 1 N hydrochloric acid, water and brine
9. dry with materialdried (MgSO4)
10. concentrationconcentrated

ORD record

ord-8187f525a87546d19e17540af87ab4a8

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09107412B2