反应详情

1-(Diphenylmethyl)-3-azetidinol hydrochloride (2.000 g, 7.29 mmol) was dissolved in methanol (75 mL) and treated with 6N HCl (1.20 mL, 7.29 mmol). Palladium hydroxide on carbon (0.200 g) was then added under a nitrogen stream. The reaction mixture was then shaken on a Parr apparatus under 40 psi of H2. After 16 h, TLC analysis (5% methanol/chloroform) revealed the starting material was consumed. The reaction mixture was filtered through Celite® and concentrated under reduced pressure to an amber oil. This material was dissolved in dimethylsulfoxide (29 mL) and the atmosphere replaced with nitrogen. Dipotassium hydrogen phosphate (5.07 g, 29.2 mmol) was added followed by 3,4-difluoronitrobenzene (0.966 mL, 8.75 mmol). The mixture was stirred at ambient temperature under nitrogen. After 3 h, TLC analysis (5% methanol/chloroform) revealed the reaction to be complete. The reaction mixture was diluted with water (250 mL) and extracted with chloroform (4×50 mL). The combined organic extracts were washed with water (2×50 mL) and brine, dried over sodium sulfate, filtered and concentrated in vacuo to give a yellow solid. Chromatography over silica gel (100 g), eluting with a gradient of 3-7% acetonitrile/chloroform afforded, after concentration of appropriate fractions, 1.00 g (65%) of the title compound as an orange solid with mp 130.5°-132° C. and MS(EI) 212 (M+).

1. customwas consumed
2. filtrationThe reaction mixture was filtered through Celite®
3. concentrationconcentrated under reduced pressure to an amber oil
4. dissolutionThis material was dissolved in dimethylsulfoxide (29 mL)
5. stirringThe mixture was stirred at ambient temperature under nitrogen
6. waitAfter 3 h
7. customthe reaction
8. extractionextracted with chloroform (4×50 mL)
9. washThe combined organic extracts were washed with water (2×50 mL) and brine
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customto give a yellow solid
14. washChromatography over silica gel (100 g), eluting with a gradient of 3-7% acetonitrile/chloroform
15. customafforded