反应详情

1-(Trifluoromethyl)cyclobutanecarboxylic acid (1 g, 5.95 mmol) and triethylamine (0.912 mL, 6.54 mmol) in anhydrous tert-butanol (20 mL) was stirred at room temperature in the presence of 4 Å molecular sieves powder. To the mixture was added diphenyl phosphorazidate (1.801 g, 6.54 mmol). The reaction mixture was refluxed under N2 for 2 days, filtered, then concentrated in vacuo. The oily residue was stirred in ether, ether layer was isolated. The procedure was repeated three times. The combined organics were washed with 5% citric acid, saturated aqueous NaHCO3 twice, brine, dried over anhydrous Na2SO4, and concentrated to give tert-butyl 1-(trifluoromethyl)cyclobutylcarbamate (713 mg) as a white solid. The solid was dissolved in 1.25 N HCl in methanol solution (10 mL), stirred at 50° C. overnight, and concentrated to give the title compound (493 mg). 1H NMR (400 MHz, DMSO-d6) δ 1.87-1.97 (m, 1H), 2.04-2.15 (m, 1H), 2.44-2.50 (m, 4H), 9.40 (br, 3H).

1. temperatureThe reaction mixture was refluxed under N2 for 2 days
2. filtrationfiltered
3. concentrationconcentrated in vacuo
4. customether layer was isolated
5. washThe combined organics were washed with 5% citric acid, saturated aqueous NaHCO3 twice
6. dry with materialbrine, dried over anhydrous Na2SO4
7. concentrationconcentrated