HCID 86700136, compound → HCID 86700137, compound

Participants

Reaction Conditions

Reaction Steps

A 3-liter flask equipped with a mechanical stirrer, addition funnel, and nitrogen inlet was charged with (E)-ethyl 2-(2-bromo-5-methyl-7-oxo-4,5-dihydrobenzo[d]thiazol-6(7H)-ylidene)acetate (24.1 g, 73 mmol, 1.0 equiv) and then diluted with THF (800 mL). To the resulting solution was added 0.6M LaCl3.2LiCl (243 mL, 146 mmol, 2.0 equiv) and then the reaction mixture was cooled to −65° C. by the aid of a dry-ice acetone bath. The addition funnel was then charged with 1.0M 4-chlorophenylmagnesium bromide (146 mL, 146 mmol, 2.0 equiv) and then slowly added to the reaction mixture over a 25 minute period. Upon completion of the addition, TLC analysis showed full consumption of the starting material (TLC of the starting material in 20% EtOAc/Hex has Rf=0.50; TLC of the product in 20% EtOAc/Hex has Rf=0.38), and the reaction was quenched with saturated NH4Cl (100 mL) and then diluted with EtOAc (1 L) and H2O (1.5 L). The cooling bath was removed and the mixture was allowed to warm to room temperature with stirring. The layers were separated and the aqueous extract was washed with EtOAc (1 L). The combined organics were dried over Na2SO4, filtered through a small plug of silica gel eluting with EtOAc, and then concentrated in vacuo. The resulting crude residue was chromatographed using a 330 g RediSep normal phase silica gel cartridge (EtOAc/Hex, 5%→15%) on a CombiFlash system to afford desired product. TLC (20% EtOAc/Hex) Rf=0.38; 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J=8.6 Hz, 2H), 7.26 (d, J=8.6 Hz, 2H), 5.62 (s, 1H), 4.57-4.40 (m, 1H), 4.22-4.04 (m, 2H), 3.03 (qd, J=16.6, 3.8 Hz, 2H), 2.61 (br s, 1H), 1.38 (d, J=7.2 Hz, 3H), 1.25 (t, J=7.1 Hz, 3H).

Provenance & Evidence