Toluene → HCID 86700136, compound

Participants

Reaction Steps

A 3.0 L round-bottom flask was charged with 2-bromo-5-methyl-5,6-dihydrobenzo[d]thiazol-7(4H)-one (75.0 g, 305 mmol, 1.00 equiv), anhydrous THF (750 mL), and a 50% w/v solution of ethylglyoxylate in toluene (211 mL, 1.07 mol, 3.50 equiv). The resulting solution was placed in a water bath. Solid lithium tert-butoxide (48.9 g, 610 mmol, 2.0 equiv) was steadily added over a 1 min period. The reaction was capped and stirred for 4.5 h. TLC (20% EtOAc/80% hexane indicated full consumption of 2-bromo-5-methyl-5,6-dihydrobenzo[d]thiazol-7(4H)-one). Saturated aqueous NH4Cl (750 mL) was added quickly. The reaction was stirred for 15 min. H2O (250 mL) was added. Most of the solids dissolved. 1.0 M aqueous HCl (180 mL) was added over a 5 min period. After a short time the pH of the aqueous layer was ˜3.5. The organic phase was collected, and the aqueous layer was extracted with EtOAc (2×375 mL). Combined organic layers were washed with brine (500 mL), dried (MgSO4), filtered, and concentrated to a minimum volume with a bath temperature of 50-60° C. and 10 mmHg vacuum. DCM (40 mL) was added. The resulting solution was transferred to a Combiflash XL solid loading cartridge by gravity loading. The solid cartridge was assembled in line with a 1.5 kg Combiflash XL silica gel column equilibrated with hexane. The following gradient elution sequence was used: [100% Hexane (5 column volumes, isocratic)→10% EtOAc/90% Hexane (10 column volumes, linear gradient)→10% EtOAc/90% Hexane (7 column volumes, isocratic))→100% EtOAc (8 column volumes, isocratic)]. Fractions containing product were combined, concentrated, and dried under high vacuum to give desired product. LCMS-ESI+ calc'd for C12H12BrNO3S: 330.0 and 332.0 (M+H+); found: 330.0 and 332.0 (M+H+). 1H NMR (400 MHz, CDCl3): δ 6.77 (s, 1H), 4.60-4.53 (m, 1H), 4.30-4.21 (m, 2H), 3.23 (dd, J=17.6, 5.8 Hz, 1H), 3.07 (d, J=5.8 Hz, 1H), 1.33 (t, J=7.2 Hz, 3H), 1.23 (d, J=7.0 Hz, 3H).

Provenance & Evidence