Formic Acid → (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-hydroxyacetate

Participants

Reaction Conditions

Reaction Steps

A 100 mL flask was charged with ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-oxoacetate (2.4 g, 5.5 mmol, 1.0 equiv) and sealed with a rubber septum. The flask was purged with argon and to this was charged ACN (11 mL) and NEt3 (1.9 mL, 13.6 mmol, 2.5 equiv) and stirring was initiated. The solution was cooled to 0° C. and then HCO2H (0.63 mL, 16.7 mmol, 3.0 equiv) was added to the solution at a rate to maintain an internal temperature not more than 20° C. Upon completion of the addition, the solution was allowed to cool back to 0° C. Argon was then bubbled through the solution using a porous gas dispersion unit. To the stirring solution at 0° C. was charged the prepared catalyst solution (0.5 mL, 0.05 equiv) from the catalyst preparation above. The solution was stirred at 0° C. with the bubbling of argon through the solution until TLC indicated complete consumption of starting material (10-18 h). The reaction was quenched with H2O then diluted with EtOAc and allowed to warm to room temperature. The layers were separated and the organic extract was washed once more with H2O. The organic extract was then dried over Na2SO4, filtered through a small pad of silica gel eluting with EtOAc, and concentrated in vacuo. The resulting crude residue was chromatographed using a 80 g RediSep normal phase silica gel cartridge (EtOAc/Hex, 5%→20%) on a CombiFlash system to give the desired product. TLC (20% EtOAc/Hex) Rf=0.27; 1H NMR (400 MHz, CDCl3) δ 7.79 (s, 1H), 7.53-7.43 (m, 2H), 7.37 (m, 2H), 5.23 (d, J=2.2 Hz, 1H), 4.19 (m, 2H), 3.29 (d, J=2.2 Hz, 1H), 2.48 (d, J=0.5 Hz, 3H), 1.21 (t, J=7.1 Hz, 3H).

Provenance & Evidence