反应详情

温度

75 °C

To tert-butyl 4-(2,2-difluoroethyl)-2-((2-oxobutyl)carbamoyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (200 mg, 0.46 mmol) in THF (2 mL) was added Burgess' salt (275 mg, 1.15 mmol) and the reaction mixture was heated at 75° C. under a nitrogen atmosphere for 2 hours. The reaction mixture was cooled to room temperature, and partitioned between EtOAc and saturated aq. NaHCO3. The layers were separated and the aqueous layer was extracted once more with EtOAc. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give an orange oil. The residue was purified by silica gel column chromatography using 0-20% EtOAc in DCM as eluent to yield tert-butyl 4-(2,2-difluoroethyl)-2-(5-ethyloxazol-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (160 mg, 84%) as a colorless oil. ESI-MS m/z calc. 415.2. found 416.5 (M+1)+; Retention time: 2.06 minutes (3 min run); 1H NMR (400 MHz, CDCl3) δ 6.69 (s, 1H), 6.06-5.68 (m, 1H), 4.89 (dd, J=10.7, 2.5 Hz, 1H), 3.85-3.58 (m, 2H), 3.37-3.01 (m, 3H), 2.87-2.59 (m, 6H), 2.45 (d, J=13.6 Hz, 1H), 2.30 (d, J=11.3 Hz, 1H), 1.65-1.48 (m, 3H), 1.45 (s, 9H), 1.25 (t, J=7.6 Hz, 3H).

1. temperatureThe reaction mixture was cooled to room temperature
2. custompartitioned between EtOAc and saturated aq. NaHCO3
3. customThe layers were separated
4. extractionthe aqueous layer was extracted once more with EtOAc
5. dry with materialThe combined organics were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto give an orange oil
9. customThe residue was purified by silica gel column chromatography