Reaction Steps
To an ice-cold solution of triphosgene (36 mg, 0.123 mmol) and triethyl amine (75 mg, 0.737 mmol) in anhydrous THF (15 mL) was added tert-butyl 2-(aminomethyl)phenylcarbamate (100 mg, 0.369 mmol) in anhydrous THF (2 mL). The reaction mixture was stirred at 0° C. for 15 min., then warmed to room temperature and concentrated to dryness. The residue was re-dissolved in anhydrous dichloromethane (15 mL), a solution of 3-isobutyl-3-phenyl-4,5,6,7-tetrahydrofuro[3,4-c]pyridin-1(3H)-one (100 mg, 0.369 mmol) (prepared according to the methods described for 3-(4-fluorophenyl)-3-isobutyl-4,5,6,7-tetrahydrofuro[3,4-c]pyridin-1(3H)-one, Scheme 1) in anhydrous dichloromethane (2 mL) was added, and the mixture stirred at room temperature for 16 hours. The reaction mixture was concentrated and purified by column chromatography (12 g, SiO2, 0 to 30% ethyl acetate in hexanes) to provide tert-butyl 2-((3-isobutyl-1-oxo-3-phenyl-1,3,4,5,6,7-hexahydrofuro[3,4-c]pyridine-5-carboxamido)methyl)phenylcarbamate as a colorless oil (68 mg, 21% yield). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.78-0.97 (m, 6H), 1.50-1.55 (m, 9H), 1.55-1.69 (m, 1H), 1.77 (dd, J=14.51, 7.35 Hz, 1H), 2.22-2.42 (m, 3H), 3.12-3.46 (m, 1H), 3.50-3.63 (m, 1H), 3.88 (d, J=18.84 Hz, 1H), 3.89-3.90 (m, 1H), 4.25-4.36 (m, 2H), 4.44 (d, J=18.84 Hz, 1H), 5.78 (d, J=5.65 Hz, 1H), 7.01 (dd, J=7.54, 1.13 Hz, 1H), 7.14-7.26 (m, 2H), 7.26-7.42 (m, 4H), 7.69 (d, J=8.29 Hz, 1H), 8.46-8.57 (m, 1H); MS m/z 542 (M+Na)+, 518 (M−H)−.
