Ethyl chloroformate → HCID 14263023, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 1 g of thebaine 1 in 20 mL of tetrahydrofuran (THF) was placed in a flame-dried round-bottom flask, and 1.92 mL (1.5 equiv) of a 2.5 M solution of N-butyllithium in hexane was added while stirring at −78° C. under nitrogen. The mixture immediately turned deep wine-red and was stirred for 45 min at −78° C. Ethyl chloroformate (0.36 mL, 1.2 equiv) was added and the mixture was stirred for 4 h at −78° C. The color changed to orange-yellow. Saturated NH4Cl (5 mL) was then added per drop and most part of the solvent was removed under reduced pressure. The residual brown product was dissolved in chloroform, washed with brine solution, dried (Na2SO4) and concentrated. The residue was subjected to column chromatography on silica gel using dichloromethane-methanol (95:5) as the eluent to isolate 0.786 g (64% yield) of 5-carbethoxythebaine 2 as a pale yellow foam. 1H NMR (CDCl3, 400 MHz): δ 6.67 d (1H, J=8.6 Hz), 6.61 d (1H, J=8.6 Hz), 5.2 d (1H, J=6.2 Hz), 5.19 d (1H, J=6.2 Hz), 4.44-4.33 m (1H), 4.28-4.16 m (1H), 3.85 s (3H), 3.66 d (1H, J=6.2 Hz), 3.57 s (3H), 3.29 d (1H, J=17.9 Hz), 2.87-2.74 m (1H), 2.7 d (1H, J=7.0 Hz), 2.68-2.57 m (1H), 2.45 s (3H), 2.16 td (1H, J=4.6, 12.5 Hz), 1.64 d (1H, J=13.3 Hz), 1.30 t (3H, J=7.0 Hz). 13C NMR (CDCl3, 100 MHz): δ 168.31, 152.64, 143.62, 142.66, 132.30, 130.56, 127.38, 119.86, 113.44, 112.09, 97.05, 95.42, 61.80, 61.26, 56.45, 55.27, 49.09, 45.49, 42.12, 31.01, 30.42, 14.21. MS (ESI): m/z 384.1 (M+1)+.

Provenance & Evidence