反应详情

温度

55 °C

To a stirred solution of 3-fluoro-3-[4-(hydroxyimino-methyl)-phenyl]-azetidine-1-carboxylic acid tert-butyl ester (0.5 g, 1.7 mmol, 1 eq) in DMF (6.5 mL) was added N-chloro succinimide (0.227 g, 1.7 mmol, 1 eq). Reaction mixture was stirred at 55° C. for 1 hour. After 1 hour (chloro intermediate formation), 1-(3,5-dichloro-4-fluoro-phenyl)-2,2,2-trifluoro-ethanone (0.45 g, 1.73 mmol, 1.02 eq) was added followed by addition of sodium bicarbonate (0.146 g, 1.74 mmol, 1.02 eq) at room temperature. Resulting reaction mixture was stirred at 55° C. for 3 hours under nitrogen atmosphere. After complete consumption of starting material, reaction mixture was quenched by water (10 mL) and extracted with ethyl acetate (3×50 mL). Combined organic phase was washed with brine solution (20 mL), dried over anhydrous Na2SO4and concentrated under reduced pressure to get brown thick oil (0.6 g, Crude). Crude was purified by Combiflash using 40 g Redisep column. Desired compound was eluted in 25% ethyl acetate in hexane to afford title compound as colorless thick oil (0.37 g, 39.32%). 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 4.16-4.24 (m, 2H), 4.38-4.47 (m, 2H), 7.59 (d, J=8.44 Hz, 2H), 7.66 (d, J=5.88 Hz, 2H), 7.89 (d, J=8.2 Hz, 2H), LC-MS (m/z): No ionization.

1. customReaction mixture
2. customResulting
3. customreaction mixture
4. stirringwas stirred at 55° C. for 3 hours under nitrogen atmosphere
5. customAfter complete consumption of starting material, reaction mixture
6. customwas quenched by water (10 mL)
7. extractionextracted with ethyl acetate (3×50 mL)
8. washCombined organic phase was washed with brine solution (20 mL)
9. customdried over anhydrous Na2SO4and
10. concentrationconcentrated under reduced pressure
11. customto get brown thick oil (0.6 g, Crude)
12. customCrude was purified by Combiflash
13. washDesired compound was eluted in 25% ethyl acetate in hexane