8-fluoro-2,3-dihydrothiochromen-4-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1M Lithium hexamethyldisilazide solution in hexane (13.2 ml) was dissolved in anhydrous tetrahydrofuran (20 ml) under nitrogen atmosphere. The solution was cooled to −78° C. 8-Fluoro-2,3-dihydro-4H-thiochromen-4-one (2.00 g, 11 mmol) was dissolved in tetrahydrofuran (40 ml), the solution was transferred to the dropping funnel and added dropwise over 30 min to the reaction mixture maintaining the temperature below −60° C. An orange clear solution was obtained which was stirred at −78° C. to −65° C. for 2 h. Methyl cyanoformate (0.935 g, 0.87 ml) was dissolved in tetrahydrofuran (2 ml) and added dropwise to the reaction solution. Stirring was continued at low temperature for 1 h, the mixture was then allowed to warm to room temperature. Saturated ammonium chloride solution (20 ml) and water (10 ml) were added, the phases mixed for 5 min and separated. The aqueous phase was washed with ethyl acetate (2×100 ml) and the combined organic phases were dried over magnesium sulphate. The mixture was filtered and the solvent removed under vacuum to give an orange oil. The crude oil was purified by column chromatography; mobile phase: hexanes, gradient to hexanes/ethyl acetate [90:10]. The title compound was isolated as a yellow solid (1.19 g, 4.95 mmol, 45%). added dropwise over 30 min to the reaction mixture maintaining the temperature below −60° C An orange clear solution was obtained which added dropwise to the reaction solution Stirring was continued at low temperature for 1 h to warm to room temperature the phases mixed for 5 min separated The aqueous phase was washed with ethyl acetate (2×100 ml) the combined organic phases were dried over magnesium sulphate The mixture was filtered the solvent removed under vacuum to give an orange oil The crude oil was purified by column chromatography

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-[(2-Fluorophenyl)sulfanyl]propanoic acid (4.0 g, 20 mmol) was mixed with concentrated sulphuric acid (20 ml) at 0–5° C. The reaction solution was stirred at 0 to 5° C. for 3 h then allowed to warm up to room temperature overnight. The mixture was quenched dropwise into ice to give a white suspension. The aqueous phase was extracted with ethyl acetate (1×200 ml, 1×100 ml). The combined organic phases were washed with saturated sodium bicarbonate solution (1×50 ml), water (1×50 ml), 1M hydrochloric acid (50 ml) and water (2×50 ml). The organic phase was dried over magnesium sulphate, filtered and concentrated under vacuum. The title compound was isolated as a yellow solid (2.10 g, 11.5 mmol, 58%). to warm up to room temperature overnight The mixture was quenched dropwise into ice to give a white suspension The aqueous phase was extracted with ethyl acetate (1×200 ml, 1×100 ml) The combined organic phases were washed with saturated sodium bicarbonate solution (1×50 ml), water (1×50 ml), 1M hydrochloric acid (50 ml) and water (2×50 ml) The organic phase was dried over magnesium sulphate filtered concentrated under vacuum