6,7-Dihydro-4H-pyrano[4,3-d]thiazol-2-ylamine hydrochloride

29943-42-8

17356-08-0

623931-31-7

1. SO2Cl2 (7.4 g, 55 mmol) was slowly added to a mixture of tetrahydro-4H-pyran-4-one (5.0 g, 50 mmol) in CCl4 (100 ml) at 0 °C. After addition, the reaction mixture was stirred at room temperature for 4 h and quenched carefully with ice-cold water. The mixture was washed well and dried over anhydrous MgSO4. The organic layer was filtered and concentrated. 2. The resulting colorless oil was dissolved in a mixed THF/EtOH solvent containing thiourea (4.0 g, 52 mmol) and refluxed for 8 hours. After completion of the reaction, it was cooled to room temperature and filtered to give 6,7-dihydro-4H-pyrano[4,3-d][1,3]thiazol-2-amine hydrochloride white solid. Yield: 4.5 g (47%); melting point: 115°C; (M+H)+: 157. 3. 6,7-Dihydro-4H-pyrano[4,3-d][1,3]thiazol-2-amine hydrochloride (4.0 g, 20.8 mmol) was dissolved in anhydrous ethanol (100 ml), sodium methanolate (1.1 g, 21 mmol) was added, and stirred for 30 min at room temperature. Ethyl bromopyruvate (10.0 g) was then added and stirred at room temperature for 2 hours and then refluxed for 48 hours. After completion of the reaction, it was cooled to room temperature and concentrated. The residue was extracted with chloroform and washed well with water. The product was purified by silica gel column chromatography with 50% ethyl acetate:hexane as eluent. A red semi-solid was obtained; yield: 3.1 g (59%); (M+H)+: 253. 4. Reduction of the ester using LiBH4 followed by oxidation of the resulting alcohol with activated MnO2, the resulting aldehyde was used in the next step of the reaction.