1-Propanol → HCID 68183039, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 6-allyl-4-(3,4-dichlorophenyl)-2-(morpholin-4-yl)-5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (0.26 g, 0.60 mmol) in 1-propanol (10.0 mL, 134 mmol) was degassed for 10 minutes. Rhodium(III)chloride, (87.0 mg g, 0.41 mmol) was added and the reaction mixture was heated to 120° C. After 18 hours, rhodium(III)chloride (59.6 mg g) was added and the mixture was stirred for additional 18 hours. The reaction was cooled to ambient temperature and quenched by the addition of a solution of saturated aqueous solution of sodium bicarbonate (10.0 mL) and extracted with EtOAc (20.0 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography (12 g cartridge, gradient hexanes to 100% EtOAc) to afford the pure product (114 mg g, 49%) as a white solid. The purified racemic mixture was separated into enantiomers on a Chiralpak IA 4.6×250 column using 70/15/15/01% Hexane/IPA/EtOH/DEA, 1.0 mL/minute for 40 minutes. Peak one (13.8 mg, 43.7%) was collected with retention time of 14.9 min. and peak two (14.8 mg, 46.9%) was collected with retention time of 21.5 min., both as a white solid. Absolute configuration of the obtained enantiomers is unknown. LCMS (AA): ES+ 383, 385, 387. 1H NMR (DMSO-d6, 400 MHz): δ 7.59 (d, J=8.4 Hz, 1H), 7.48 (d, J=2.4 Hz, 1H), 7.35 (br s, 1H), 5.88 (s, 1H), 4.19 (t, J=5.6 Hz, 1H), 3.69-3.63 (m, 5H), 3.37 (ddd, J=12.4, 6.0, 3.2 Hz, 1H), 3.13-3.11 (m, 4H).

Provenance & Evidence