METHYL 4-[(4-CHLOROPHENYL)SULFONYL]-3-METHYLTHIOPHENE-2-CARBOXYLATE synthesis

Yield:721943-09-5 87%

Reaction Conditions:

with diisobutylaluminium hydride in tetrahydrofuran;dichloromethane at 0; for 5 h;

Steps:

[4- (4-CHLORO-BENZENESULFONYL)-3-METHYL-THIOPHEN-2-YL)-METHANOL.

A solution OF 4- (4-CHLORO-BENZENESULFONYL)-3-METHYL-THIOPHENE-2-CARBOXYLIC acid methyl ester (992 mg, 3.00 mmol) in dry tetrahydrofuran (20 ML) and dry CH2C12 (10 mL) was cooled to 0 °C under N2, and DIBAL-H (9.0 ML, 9.0 mmol, 1 M solution in toluene) was added. After 3 hours, another portion of DIBAL-H (4.5 mL, 4.5 mmol) was added, and stirring was continued for another 2 hours. The reaction was quenched by the addition of saturated Rochelle salt solution (30 mL), and the mixture was stirred for 1 hour at room temperature. The phases were separated, the aqueous phase was extracted with EtOAc (2 x 50 mL) and the pooled organic layers were dried over NA2S04 and evaporated in vacuo. The product was purified by chromatography on silica gel on a FlashMaster system using as eluent heptane/ethyl acetate (linear gradient elution from 1: 0 to 6: 4). Fractions containing the product were pooled and evaporated in vacuo to yield the desired compound (788 mg, 87%).

References:

WO2004/58739,2004,A1 Location in patent:Page 45; 53