反应详情

To a stirring solution of potassium tert-butoxide (7.23 mL of 1 M, 7.23 mmol) in tetrahydrofuran (20 mL) at 70° C. was added a solution of tert-butyl 4-[[(2-bromo-2,2-difluoro-acetyl)amino]methyl]-4-hydroxy-piperidine-1-carboxylate (1.4 g, 3.62 mmol) in tetrahydrofuran (20 mL) over 15 min. After 20 min the reaction mixture was diluted with 1:1 brine/saturated NH4Cl and ethyl acetate. The organic layer was separated, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Silica gel chromatography (40 g silica, 30-100% ethyl acetate/hexane, product visualized by TLC with ninhydrin staining+heat) provided tert-butyl 4,4-difluoro-3-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate (340 mg, 1.11 mmol, 31%) as a white solid. ESI-MS m/z calc. 306.1. found 307.5 (M+1)+; Retention time: 1.32 minutes (3 min run). 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 3.75 (d, J=13.3 Hz, 2H), 3.45 (d, J=3.2 Hz, 2H), 3.07 (br s, 2H), 1.79 (d, J=13.6 Hz, 2H), 1.72-1.60 (m, 2H), 1.41 (s, 9H).

1. customThe organic layer was separated
2. washwashed with brine
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. temperatureSilica gel chromatography (40 g silica, 30-100% ethyl acetate/hexane, product visualized by TLC with ninhydrin staining+heat)