反应详情

温度

110 °C

A mixture of 1,1-dimethylethyl 4-({[6-(4-bromo-2-fluorophenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate (0.214 g, 0.46 mmol), methanesulfinic acid sodium salt (71 mg, 80%, 0.55 mmol), L-proline (11 mg, 0.09 mmol), Cul (9 mg, 0.05 mmol) and NaOH (4 mg, 0.09 mmol) in DMSO (2.5 mL) was degassed, purged with N2 and heated at 110° C. for 48 h. The mixture was cooled to ambient temperature and was poured into water and extracted with EtOAc. The combined organic extract was washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a yellow solid. The crude product was purified by chromatography on a silica gel column eluted with 25% EtOAc/CH2Cl2 to give 62.5 mg (29%) of the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.40 (d, 1H, J=3.0 Hz), 8.15-8.10 (m, 1H), 7.90-7.75 (m, 3H), 7.50 (dd, 1H, Ja=8.8 Hz, Jb=2.9 Hz), 4.20-4.10 (m, 2H), 4.00 (d, 2H, J=6.4 Hz), 3.18 (s, 3H), 2.90-2.75 (m, 2H), 2.15-2.00 (m, 1H), 1.90-1.80 (m, 2H), 1.46 (s, 9H), 1.40-1.25 (m, 2H); LRMS (ESI), m/z 465 (M+H).

1. customwas degassed
2. custompurged with N2
3. temperatureThe mixture was cooled to ambient temperature
4. additionwas poured into water
5. extractionextracted with EtOAc
6. extractionThe combined organic extract
7. washwas washed with water and brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationthe filtrate was concentrated
11. customto give the crude product as a yellow solid
12. customThe crude product was purified by chromatography on a silica gel column
13. washeluted with 25% EtOAc/CH2Cl2