Lithium hexamethyldisilazane → tert-Butyl {(3S,5S)-5-(2,3-difluorophenyl)-2-oxo-1-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]piperidin-3-yl}carbamate

温度

-30 °C

To a pre-cooled −30° C. solution of tert-butyl[(3S,5S)-5-(2,3-difluorophenyl)-2-oxopiperidin-3-yl]carbamate (described in Intermediate 11, step B, 56 mg, 0.172 mmol) in tetrahydrofuran:N-methyl-2-pyrrolidinone (2:1, 0.8 mL) was added lithium bis(trimethylsilyl)amide (0.22 mL, 0.22 mmol, 1 M in THF) and the mixture was stirred at −30° C. for 30 min. (2S)-2-(Trifluoromethyl)oxirane (19 mg, 0.172 mmol) was added and the resulting mixture was stirred at −30° C. for 2 h. The mixture was diluted with water and extracted with ethyl acetate (3×). The combined organic extracts were washed with water, brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (0% ethyl acetate→90% ethyl acetate/hexane) afforded the title compound. MS: m/z=461.2 (M+Na).

1. additionwas added
2. extractionextracted with ethyl acetate (3×)
3. washThe combined organic extracts were washed with water, brine
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customPurification by silica gel chromatography (0% ethyl acetate→90% ethyl acetate/hexane)

ORDレコード

ord-9c09d843f6e3479182a07bb2d890fac2

出典データセット

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08481556B2