(+-)-Methionine → HCID 68226904, compound

Participants

Reaction Steps

A mixture containing 11b-ethyl-9-methoxy-1,2,5,6,7,11b-hexahydro-dibenzo[a,c]cyclohepten-3-one (10.2 g, 37.7 mmol) [prepared as described in US2012/238549 A1] and DL-methionine (18.3 g, 123 mmol) in methanesulfonic acid (100 mL, 1.54 mol) was mechanically stirred under nitrogen at rt over about 3 days. The reaction was diluted with DCM (700 mL) and poured carefully onto ice water (700 mL). The layers were separated and the aqueous layer was extracted again with DCM (500 mL). The combined organic layers were washed with water (2×500 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (220 g) using a gradient from 0-50% EtOAc in DCM. Product fractions were combined and concentrated under reduced pressure to yield 11b-ethyl-9-hydroxy-1,2,5,6,7,11b-hexahydro-dibenzo[a,c]cyclohepten-3-one (17, R2=Ethyl) (8.54 g, 88%) as an off-white solid. LC/MS, method 1, 0.73 min, 319 (M+H)+. 1H NMR (400 MHz, DMSO) δ 9.19 (s, 1H), 7.11 (d, J=8.6 Hz, 1H), 6.62 (dd, J=8.5, 2.7 Hz, 1H), 6.51 (d, J=2.7 Hz, 1H), 5.81 (s, 1H), 2.79-2.70 (m, 1H), 2.67-2.52 (m, 1H), 2.44-2.35 (m, 2H), 2.33-2.18 (m, 3H), 2.14-2.04 (m, 1H), 2.01-1.90 (m, 1H), 1.86-1.66 (m, 3H), 0.78 (t, J=7.4 Hz, 3H).

Provenance & Evidence