反应详情

To a cooled (ice-water bath) solution of tert-butyl 6,6-difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ylcarbamate (190 mg, 0.51 mmol) in THF (10 mL) was added lithium hexamethyldisilazide (1M in THF, 0.8 mL, 0.8 mmol) and the mixture stirred for 30 min. Iodomethane (0.06 mL, 1.02 mmol) was added and the mixture stirred at room temperature for 16 hr. Water (2 mL) was added and the mixture extracted with EtOAc (30 mL). The organic layer was separated, dried over Na2SO4 and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-70% EtOAc/isohexane) gave tert-butyl 6,6-difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-yl(methyl)carbamate (180 mg, 90%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.09-7.99 (m, 1H), 4.57-4.38 (m, 1H), 3.85 (s, 3H), 3.84-3.53 (m, 1H), 3.45-3.15 (m, 3H), 2.81 (s, 3H), 2.53-2.29 (m, 2H), 2.16-2.01 (m, 2H), 1.48 (s, 9H).

1. stirringthe mixture stirred at room temperature for 16 hr
2. extractionthe mixture extracted with EtOAc (30 mL)
3. customThe organic layer was separated
4. dry with materialdried over Na2SO4
5. customthe solvent removed under reduced pressure
6. customPurification via silica gel column chromatography (0-70% EtOAc/isohexane)