1,3-Dichloroacetone → Methyl 3-[4-(hydroxymethyl)-1,3-thiazol-2-yl]benzoate

Participants

Reaction Conditions

Reaction Steps

The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) A mixture of 3-thiocarbamoyl-benzoic acid methyl ester [CAS-No. 106748-27-0] (7.8 g), 1,3-dichloro-2-propanone (8.4 g) and sodium bicarbonate (8.4 g) in 1,4-dioxane (180 mL) was heated to 60° C. for 24 h. The reaction mixture was cooled to 20° C. and added to a stirred solution of sodium methoxide (5.4 g) in methanol (200 mL). Stirring was continued for 0.5 h. The mixture was poured into ice-cold 2N HCl (200 mL) and the product was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuum. The residue was crystallized from dichloromethane/hexane to give 3-(4-hydroxymethyl-thiazol-2-yl)-benzoic acid methyl ester (7.5 g) as light-brown crystals, 115-117 °C. ii.) A mixture of this material (7.5 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0.19 g) in ethyl acetate (50 mL) was stirred at 20 ° C. for 1 h. The solution was diluted with ethyl acetate, washed with 5% sodium bicarbonate solution and with brine, dried over sodium sulfate and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using ethyl acetate/hexane (1:2) as eluent to give (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (9.6 g) as a pale-yellow oil.] (3.5 g, 11 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a pale yellow oil (3.8 g).

Provenance & Evidence