反应详情

A mixture of 4-bromo-1H-pyrazole (200 mg, 1.36 mmol), methyl 4-(1-hydroxyethyl)benzoate (490 mg, 2.72 mmol), and triphenylphosphine (resin bound: 3 mmol/g loading, 907 mg, 2.72 mmol) in THF (5 mL) was stirred for 5 minutes at ambient temperature. Di-tert-butyl azodicarboxylate (627 mg, 2.72 mmol) was added and the reaction mixture was stirred for 24 hours at ambient temperature. The reaction mixture was filtered, and the filtrate was diluted with dichloromethane (25 mL) and TFA (6 mL) and stirred for 30 minutes. The mixture was concentrated under reduced pressure and then diluted with ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL). The organic layer was separated, washed with brine (25 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford the crude product residue. The crude product residue was purified by column chromatography on silica (0-100% diethyl ether/hexanes) to afford methyl 4-(1-(4-bromo-1H-pyrazol-1-yl)ethyl)benzoate. MS ESI calc'd. for C13H14BrN2O2 [M+H]+ 309 and 311. found 309 and 311. 1H NMR (500 MHz, DMSO-d6) δ 8.17 (s, 1H), 7.90 (dd, J=6.5 Hz, 1.5 Hz, 2H), 7.58 (s, 1H), 7.33 (d, J=8.5 Hz, 2H), 5.72-5.65 (m, 1H), 3.82 (s, 3H), 1.78 (d, J=7.5 Hz, 3H).

1. stirringthe reaction mixture was stirred for 24 hours at ambient temperature
2. filtrationThe reaction mixture was filtered
3. additionthe filtrate was diluted with dichloromethane (25 mL) and TFA (6 mL)
4. stirringstirred for 30 minutes
5. concentrationThe mixture was concentrated under reduced pressure
6. additiondiluted with ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL)
7. customThe organic layer was separated
8. washwashed with brine (25 mL)
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customto afford the crude product residue
13. customThe crude product residue was purified by column chromatography on silica (0-100% diethyl ether/hexanes)