4-Methylbenzenethiol → 4-(5-Methyl-4-(tosylmethyl)oxazol-2-yl)-N-(pyridin-3-ylmethyl)benzamide

Participants

Reaction Conditions

Reaction Steps

A solution of alcohol 56 (163 mg, 0.5 mmol) in anhydrous DMF (7 mL) was cooled to 0° C. NEt3 (0.14 mL, 1 mmol) and MsCl (47 λL, 0.6 mmol) were added successively and the reaction mixture was stirred at 0° C. for 1 h. K2CO3 (138 mg, 1 mmol) and 4-methylthiophenol (68 mg, 0.55 mmol) were added and the reaction mixture was stirred at 60° C. for 1 h. The reaction mixture was then cooled to 20° C. and partitioned between EtOAc (200 mL) and H2O (50 mL). The organic fraction was washed with H2O (2×50 mL), washed with brine (50 mL), and dried. The solvent was evaporated to give the crude sulfide (158 mg, 0.37 mmol) which was used without further purification. A solution of Oxone® (172 mg, 0.28 mmol) in H2O (3 mL) was added at 0° C. to a stirred solution of crude sulfide (88 mg, 0.2 mmol) in MeOH (3 mL), and the reaction mixture was stirred for 1 h at 20° C. H2O was added (50 mL), the mixture was extracted with DCM (3×50 mL) and the organic phase was washed with brine (50 mL), dried, and the solvent was evaporated. Remaining sulfide (70 mg, 0.16 mmol) was treated as described and the combined crude products were purified by column chromatography, eluting with 5% MeOH/EtOAc, to give sulfone 9 (65 mg, 28%) as a white powder: spectroscopically identical to the sample prepared above.

Provenance & Evidence