2,2,2-trifluoroethanethioamide

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of ethyl 3-chloro-2-oxo-3-phenylpropanoate and trifluorothioacetamide in MeCN was heated under reflux. To the reaction mixture was added an aqueous Na2CO3 solution, followed by extraction with EtOAc. The organic layer was washed with water and brine in this order, dried, and then concentrated under reduced pressure. The residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, hexane: EtOAc) to obtain ethyl 5-phenyl-2-(trifluoromethyl)-1,3-thiazole-4-carboxylate as a white solid. under reflux followed by extraction with EtOAc The organic layer was washed with water and brine in this order dried concentrated under reduced pressure The residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, hexane: EtOAc)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 11.22g of 2,2,2,-trifluorothioacetamide and 10.14g of ethyl 2-chloro-2-formylacetate was stirred for 30 minutes in an oil bath of 70° C. and then for 1.5 hours in an oil bath of 100° C., to which 100ml of dichloromethane were added. After removing an insoluble substance, the mixture was concentrated and the residue was subjected to a column chromatography [developing solvent: hexane-ethyl acetate (10:1)], to obtain 3.74g of ethyl 2-(trifluoromethyl)-5-thiazolecarboxylate as yellow liquid. for 1.5 hours in an oil bath of 100° C. After removing an insoluble substance the mixture was concentrated

反応条件: temp:34.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 3L 4-neck RBF equipped with a mechanical stirrer, reflux condenser, thermometer and addition funnel was charged 358 g of ethyl chlorotrifluoroacetoacetate (1.64 moles), 2,2,2-trifluorothioacetamide and 1000 mL of acetonitrile. To this mixture was added 331.9 g of triethylamine (2.0 eq, 3.28 moles) dropwise over 2.5 hours. During the addition the temperature was maintained at 30-38° C. and upon completion of the addition the reaction was heated to reflux for 2 hours and stirred overnight at room temperature. The reaction mixture was filtered and the resulting filtrate was concentrated by rotary evaporation to provide an oily solid which was dissolved in 1500 mL of ethyl acetate. This was washed with 2×500 mL of water, 1×500 mL of brine and concentrated by rotary evaporation to yield 356.6 g of ethyl 2,4-bis-trifluoromethyl-5-thiazole carboxylate which was purified by distillation. reflux condenser thermometer and addition funnel During the addition the temperature was heated to reflux for 2 hours The reaction mixture was filtered the resulting filtrate was concentrated by rotary evaporation to provide an oily solid which This was washed with 2×500 mL of water, 1×500 mL of brine concentrated by rotary evaporation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 2,2,2-trifluoroethanethioamide (200 mg) and t-BuOH (10 mL) was added ethyl 2-chloro-3-oxobutanoate (0.217 mL) at room temperature. The mixture was refluxed for 2 days. After cooling, EtOAc was poured into the mixture, and the mixture was washed successively with water and brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (NH, EtOAc/hexane) to give the title compound (133 mg). The mixture was refluxed for 2 days After cooling the mixture was washed successively with water and brine dried over Na2SO4 concentrated in vacuo The residue was purified by silica gel column chromatography (NH, EtOAc/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 2,2,2-trifluoroethanethioamide (200 mg) and t-BuOH (10 mL) was added ethyl 2-chloro-3-oxobutanoate (0.217 mL) at room temperature. The mixture was refluxed for 2 days. After cooling, EtOAc was poured into the mixture, and the mixture was washed successively with water and brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (NH, EtOAc/hexane) to give the title compound (133 mg). The mixture was refluxed for 2 days After cooling the mixture was washed successively with water and brine dried over Na2SO4 concentrated in vacuo The residue was purified by silica gel column chromatography (NH, EtOAc/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of ethyl 3-chloro-2-oxo-3-phenylpropanoate and trifluorothioacetamide in MeCN was heated under reflux. To the reaction mixture was added an aqueous Na2CO3 solution, followed by extraction with EtOAc. The organic layer was washed with water and brine in this order, dried, and then concentrated under reduced pressure. The residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, hexane: EtOAc) to obtain ethyl 5-phenyl-2-(trifluoromethyl)-1,3-thiazole-4-carboxylate as a white solid. under reflux followed by extraction with EtOAc The organic layer was washed with water and brine in this order dried concentrated under reduced pressure The residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, hexane: EtOAc)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of ethyl 3-chloro-2-oxo-3-phenylpropanoate and trifluorothioacetamide in MeCN was heated under reflux. To the reaction mixture was added an aqueous Na2CO3 solution, followed by extraction with EtOAc. The organic layer was washed with water and brine in this order, dried, and then concentrated under reduced pressure. The residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, hexane: EtOAc) to obtain ethyl 5-phenyl-2-(trifluoromethyl)-1,3-thiazole-4-carboxylate as a white solid. under reflux followed by extraction with EtOAc The organic layer was washed with water and brine in this order dried concentrated under reduced pressure The residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, hexane: EtOAc)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 11.22 g of 2,2,2,-trifluorothioacetamide and 10.14 g of ethyl 2-chloro-2-formylacetate was stirred for 30 minutes in an oil bath of 70° C. and then for 1.5 hours in an oil bath of 100° C., to which 100 ml of dichloromethane were added. After removing an insoluble substance, the mixture was concentrated and the residue was subjected to a column chromatography [developing solvent: hexane-ethyl acetate (10:1)], to obtain 3.74 g of ethyl 2-(trifluoromethyl)-5-thiazolecarboxylate as yellow liquid. for 1.5 hours in an oil bath of 100° C. After removing an insoluble substance the mixture was concentrated

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 11.22 g of 2,2,2,-trifluorothioacetamide and 10.14 g of ethyl 2-chloro-2-formylacetate was stirred for 30 minutes in an oil bath of 70° C. and then for 1.5 hours in an oil bath of 100° C., to which 100 ml of dichloromethane were added. After removing an insoluble substance, the mixture was concentrated and the residue was subjected to a column chromatography [developing solvent: hexane-ethyl acetate (10:1)], to obtain 3.74 g of ethyl 2-(trifluoromethyl)-5-thiazolecarboxylate as yellow liquid. for 1.5 hours in an oil bath of 100° C. After removing an insoluble substance the mixture was concentrated

反応条件: temp:34.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 3 L 4-neck RBF equipped with a mechanical stirrer, reflux condenser, thermometer and addition funnel was charged 358 g of ethyl chlorotrifluoroacetoacetate (1.64 moles), 2,2,2-trifluorothioacetamide and 1000 mL of acetonitrile. To this mixture was added 331.9 g of triethylamine (2.0 eq, 3.28 moles) dropwise over 2.5 hours. During the addition the temperature was maintained at 30-38° C. and upon completion of the addition the reaction was heated to reflux for 2 hours and stirred overnight at room temperature. The reaction mixture was filtered and the resulting filtrate was concentrated by rotary evaporation to provide an oily solid which was dissolved in 1500 mL of ethyl acetate. This was washed with 2×500 mL of water, 1×500 mL of brine and concentrated by rotary evaporation to yield 356.6 g of ethyl 2,4-bis-trifluoromethyl-5-thiazole carboxylate which was purified by distillation. To a 3 L 4-neck RBF equipped with a mechanical stirrer reflux condenser thermometer and addition funnel During the addition the temperature was heated to reflux for 2 hours The reaction mixture was filtered the resulting filtrate was concentrated by rotary evaporation to provide an oily solid which This was washed with 2×500 mL of water, 1×500 mL of brine concentrated by rotary evaporation

反応条件: temp:34.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 3 L 4-neck RBF equipped with a mechanical stirrer, reflux condenser, thermometer and addition funnel was charged 358 g of ethyl chlorotrifluoroacetoacetate (1.64 moles), 2,2,2-trifluorothioacetamide and 1000 mL of acetonitrile. To this mixture was added 331.9 g of triethylamine (2.0 eq, 3.28 moles) dropwise over 2.5 hours. During the addition the temperature was maintained at 30-38° C. and upon completion of the addition the reaction was heated to reflux for 2 hours and stirred overnight at room temperature. The reaction mixture was filtered and the resulting filtrate was concentrated by rotary evaporation to provide an oily solid which was dissolved in 1500 mL of ethyl acetate. This was washed with 2×500 mL of water, 1×500 mL of brine and concentrated by rotary evaporation to yield 356.6 g of ethyl 2,4-bis-trifluoromethyl-5-thiazole carboxylate which was purified by distillation. To a 3 L 4-neck RBF equipped with a mechanical stirrer reflux condenser thermometer and addition funnel During the addition the temperature was heated to reflux for 2 hours The reaction mixture was filtered the resulting filtrate was concentrated by rotary evaporation to provide an oily solid which This was washed with 2×500 mL of water, 1×500 mL of brine concentrated by rotary evaporation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2,2-Trifluoroethanethioamide (which may be prepared by the method of J. H. Hillhouse et al., Phosphorus, Sulfur Relat. Elem. 1986, 26, 169-84) (157 mg, 1.22 mmol) in ethanol (1.3 mL) was added drop-wise to a solution of 2-bromo-1-(2-hydroxyphenyl)ethanone (119 mg, 0.55 mmol) in ethanol (1.3 mL) and the reaction was refluxed overnight. The reaction was concentrated in vacuo and purified via silica gel chromatography (Gradient: 5% to 20% ethyl acetate in heptane) to afford the title compound. Yield: 67 mg, 0.27 mmol, 49%. LCMS m/z 246.0 (M+1). 1H NMR (400 MHz, CDCl3) δ 6.95 (ddd, J=8, 7, 1 Hz, 1H), 7.07 (dd, J=8.2, 1.2 Hz, 1H), 7.33 (ddd, J=8, 7, 2 Hz, 1H), 7.64 (dd, J=7.8, 1.6 Hz, 1H), 7.81 (s, 1H), 10.47 (s, 1H). the reaction was refluxed overnight The reaction was concentrated in vacuo purified via silica gel chromatography (Gradient: 5% to 20% ethyl acetate in heptane)