Carbon Disulfide → HCID 178527855, compound

Participants

Reaction Conditions

Reaction Steps

2-amino-1-(4-chlorophenyl)ethanone hydrochloride (0.80 g, 3.88 mmol) and carbon disulfide (0.47 mL, 0.59 g, 7.76 mmol) was suspended in ethanol (10 mL). To this was slowly added a solution of sodium carbonate (0.44 g, 4.08 mmol) in water (4 mL) at ambient temperature. After heating to 80° C. ext. temp. for 18 h the cold mixture was filtered. The filtrate was diluted with acetic acid (40 mL) and stirred for 15 min. at room temperature. Evaporation of the solvents in vacuo gave 1.42 g of a crude 5-(4-chlorophenyl)oxazole-2-thiol which was of ca. 61% purity (HPLC-MS) and used as is in the next step. The crude oxazole-2-thiol compound (1.42 g, max. 3.88 mmol) was suspended in phosphorous oxychloride (5 mL). To this was added dropwise triethyl amine (1.15 mL, 0.84 mg, 8.27 mmol) and the mixture heated to 105° C. ext. temperature for 4 h. The reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (3×40 mL). The combined organic layers were washed with aq. sat. bicarbonate (100 mL) and water (50 mL). Drying (sodium sulfate) and concentration in vacuo yielded crude product (615 mg), which was purified by column chromatography (SiO2, 5-40% ethyl acetate in heptanes) to give pure 2-chloro-5-(4-chlorophenyl)oxazole (105 mg, 0.49 mmol, 13%, purity 96% HPLC-MS).

Provenance & Evidence