Dichloromethane → (S)-2-(5-chloro-2-((1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamido) phenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-yl 1-chloroethyl carbonate

Participants

Reaction Conditions

Reaction Steps

A solution of (1S,4R)-N-(4-chloro-2-((S)-4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide (10, 20 g, 42.6 mmol), dichloromethane (100 mL) and triethylamine (5.17 g, 51.1 mmol) was stirred at 0-5° C. for 20 minutes, then 1-chloroethyl chloroformate (7.3 g, 51.1 mmol) was added dropwise. The mixture was stirred at 5-10° C. for 1 hour. Water (60 ml) was added with stirring and then the layers were separated. The organic solution was concentrated and MTBE (180 ml) was added. After washing with water twice, the system was concentrated to 30 ml and then MTBE (10 ml) and hexane (60 ml) were added. The suspension was stirred at 70° C. for 30 min and filtered to give (S)-2-(5-chloro-2-((1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamido)phenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-yl 1-chloroethyl carbonate (7, R1 is 4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptyl, R3 is 1-chloroethyl) as a white solid. 1H NMR (CDCl3) δ9.43, 9.30 (s, 1H), 8.17, 8.06 (d, J=8.7 Hz, 1H), 7.62, 7.54 (s, 1H), 7.42 (d, J=8.7 Hz, 1H), 6.36 (q, J=5.7 Hz, 1H), 2.60-2.50 (m, 1H), 2.09-1.93 (m, 2H), 1.89-1.86 (at, J=4.5 Hz, 3H), 1.77-1.61 (m, 2H), 1.16 (d, J=10.5 Hz, 6H), 1.01 (d, J=7.5 Hz, 3H), 0.97-0.92 (m, 2H), 0.88-0.84 (m, 2H).

Provenance & Evidence