5,5-diethoxy-1,1,1-trifluoropent-3-yn-2-one

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

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5,5-Diethoxy-1,1,1-trifluoro-pent-3-yn-2-one (2 g, 8.9 mmol) and 2-hexyl-isothiourea hydrobromide (2.4 g, 9.8 mmol) were dissolved under nitrogen in THF (20 mL). Then triethylamine (2.7 mL, 19.6 mmol) was added slowly. The reaction was exothermic (40° C.). The suspension was stirred for 4 h at 20° C. The product was extracted with AcOEt, sat. NH4Cl solution, dried and concentrated. The residue was purified by silica gel chromatography in heptane/AcOEt 20:1. One obtained 2.5 g (76%) of a colorless oil. MS: m/z=367 (M+H). (40° C.) The product was extracted with AcOEt, sat. NH4Cl solution dried concentrated The residue was purified by silica gel chromatography in heptane/AcOEt 20:1

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,3-Diethoxy-1-propyne (10 mL, 70 mmol) was dissolved under argon in THF (200 mL) and cooled to −70° C. Then a 1.6 M solution of n-butyllithium in hexane (48 mL, 77 mmol) was added slowly at −70° C., then allowed to warm to −30° C. and stirred at −30° C. for 30 min, then cooled again to −70° C. Ethyl trifluoroacetate (9.2 mL, 77 mmol) was added in one portion at −70° C. (the temperature rose to −50°) then stirred without cooling until −30° C. was reached, then quenched with sat. NH4Cl solution (20 mL). Extraction: 2×AcOEt, 1× sat. NH4Cl sat., 1× sat. NaCl. Chromatography on silica gel in heptane/ethyl acetate 5:1 afforded 4.94 g (31%) of an orange oil. GC/MS: m/z=223 (M−H). to warm to −30° C. cooled again to −70° C rose to −50° then stirred without cooling until −30° C. quenched with sat. NH4Cl solution (20 mL) Extraction

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 5,5-Diethoxy-1,1,1-trifluoro-pent-3-yn-2-one (2.16 g, 9.64 mmol) in THF (30 ml) was cooled to 0° C. (ice bath). Methyl thioglycolate (0.88 ml, 9.64 mmol) was added in one portion and the mixture was stirred at 0° C. for 1.5 h. Methanol (6 ml) and Cs2CO3/MgSO4 (2 g/4 g, pre-dried at 200° C. in vacuum) were added at 0° C. The mixture was stirred at 0° C. for 15 min and then at rt for 15 h. The reaction mixture was quenched by pouting into EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography with 0-30% EtOAc in hexane to afford the desired product (1.90 g, 63% yield). The mixture was stirred at 0° C. for 15 min at rt for 15 h The reaction mixture was quenched The organic layer was washed with brine dried over Na2SO4 concentrated under reduced pressure The residue was purified by flash chromatography with 0-30% EtOAc in hexane

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

Procedure: A mixture of 3,3-Diethoxy-propyne (0.98 g, 7.64 mmol) in THF (20 ml) was cooled to −78 C under Ar. A solution of n-BuLi (2.0M in cyclohexane, 4.2 ml, 8.40 mmol) was added. After 30 min., Trifluoroacetic acid ethyl ester (1.19 g, 8.40 mmol) was added. After 1 h, the reaction was quenched by dilution with 1N HCl, warmed to room temperature and extracted into EtOAc. The organic layer was washed with brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography (0-40% EtOAc in Hexanes) to give product, 0.51 g (30%). was cooled to −78 C under Ar After 1 h the reaction was quenched by dilution with 1N HCl extracted into EtOAc The organic layer was washed with brine dried over sodium sulfate filtered evaporated The residue was purified by flash chromatography (0-40% EtOAc in Hexanes) to give product, 0.51 g (30%)

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5,5-Diethoxy-1,1,1-trifluoro-pent-3-yn-2-one (2 g, 8.9 mmol) and 2-hexyl-isothiourea hydrobromide (2.4 g, 9.8 mmol) were dissolved under nitrogen in THF (20 mL). Then triethylamine (2.7 mL, 19.6 mmol) was added slowly. The reaction was exothermic (40° C.). The suspension was stirred for 4 h at 20° C. The product was extracted with AcOEt, sat. NH4Cl solution, dried and concentrated. The residue was purified by silica gel chromatography in heptane/AcOEt 20:1. One obtained 2.5 g (76%) of a colorless oil. MS: m/z=367 (M+H). (40° C.) The product was extracted with AcOEt, sat. NH4Cl solution dried concentrated The residue was purified by silica gel chromatography in heptane/AcOEt 20:1

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,3-Diethoxy-1-propyne (10 mL, 70 mmol) was dissolved under argon in THF (200 mL) and cooled to −70° C. Then a 1.6 M solution of n-butyllithium in hexane (48 mL, 77 mmol) was added slowly at −70° C., then allowed to warm to −30° C. and stirred at −30° C. for 30 min, then cooled again to −70° C. Ethyl trifluoroacetate (9.2 mL, 77 mmol) was added in one portion at −70° C. (the temperature rose to −50°) then stirred without cooling until −30° C. was reached, then quenched with sat. NH4Cl solution (20 mL). Extraction: 2×AcOEt, 1× sat. NH4Cl sat., 1× sat. NaCl. Chromatography on silica gel in heptane/ethyl acetate 5:1 afforded 4.94 g (31%) of an orange oil. GC/MS: m/z=223 (M−H). to warm to −30° C. cooled again to −70° C rose to −50° then stirred without cooling until −30° C. quenched with sat. NH4Cl solution (20 mL) Extraction