反应详情

温度

120 °C

To a Smith microwave vial was added (2R,5S)-2-[4-(2-fluoro-5-hydroxy-phenyl)-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one (which may be prepared as described in Description 134) (66.5 mg, 0.1900 mmol), triphenyl phosphine (102.19 mg, 0.3900 mmol), Di-tert-butyl azodicarboxylate ((89.71 mg, 0.3900 mmol) and 2-fluoroethanol (0.02 mL, 0.2900 mmol) in THF (0.5000 mL). Toluene (1 mL) was added. The reaction mixture was heated by microwave at 120° C. for 45 min. The reaction mixture was eluted on an SCX-2 cartrige (0.5 g) and washed with DCM followed MeOH. The desired product was eluted off the cartridge with ammonia in MeOH (0.2M). Evaporation of solvents gave colourless oil. The crude residue was purified by silica gel chromatography (KPNH silica 11 g) eluting with ethyl acetate in iso-hexane (10-100%) followed by methanol in ethyl acetate (0-18%). Evaporation of desired fractions gave colourless oil. It was further purified by a ChiralPak IA column eluting with ethanol/n-heptane (20%:80%) to give 2R,5S)-2-[4-[2-fluoro-5-(2-fluoroethoxyl)phenyl]-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;

1. washThe reaction mixture was eluted on an SCX-2 cartrige (0.5 g)
2. washwashed with DCM
3. washThe desired product was eluted off the cartridge with ammonia in MeOH (0.2M)
4. customEvaporation of solvents
5. customgave colourless oil
6. customThe crude residue was purified by silica gel chromatography (KPNH silica 11 g)
7. washeluting with ethyl acetate in iso-hexane (10-100%)
8. customEvaporation of desired fractions
9. customgave colourless oil
10. customIt was further purified by a ChiralPak IA column
11. washeluting with ethanol/n-heptane (20%:80%)