(3-acetyloxy-2-oxopropyl) acetate

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

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: An ethynylmagnesium bromide solution (0.5 M in THF) was cooled to −78° C. under nitrogen. A solution of 1,3-diacetoxyacetone (0.5 g) in THF (3.0 mL) was added, and the resulting mixture was stirred for 30 min at −78° C., then at 0° C. for 5 min, quenched with 1.0 N aq. HCl (3 mL) and extracted in EtOAc. Evaporation gave crude 2-ethynyl-2-hydroxypropane-1,3-diyl diacetate, contaminated with about 50 mol % of 1,3-dacetoxyacetone. The crude material was used without further purification. at 0° C. for 5 min quenched with 1.0 N aq. HCl (3 mL) extracted in EtOAc Evaporation

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

Procedure: Under an atmosphere of argon, 90 g of 1,3-dihydroxyacetone dimer and 250 mg of 4-(N,N-dimethylamino)pyridine were dissolved in 250 ml of pyridine. To the resulting solution, 225 ml of acetic anhydride was added droopowise at room temperature over 1 hour. After the resulting liquid was stirred at room temperature for 30 minutes, thereto was added 50 ml of methanol and the resulting liquid was further stirred at room temperature for 30 minutes. The solvent was removed under reduced pressure and the residue was subjected to a recrystallization from ether-petroleum ether to give 190 g of the desired compound. the resulting liquid was further stirred at room temperature for 30 minutes The solvent was removed under reduced pressure the residue was subjected to a recrystallization from ether-petroleum ether

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an atmosphere of argon, 22.5 g of 2,4-difluorobromobenzene was dissolved in 200 ml of diethyl ether and to the resulting solution was added dropwise 73 ml of 1.63M n-hexane solution of n-butyllithium at -30° C. The resulting liquid was stirred for 1 hour and stored at -60° C. This liquid was carefully added dropwise using an injection cylinge to 150 ml of diethyl ether solution of 17.4 g of 1,3-diacetoxyacetone which was previously cooled to -30° C. After the resulting liquid was stirred at -60° C. for 2 hours, a temperature thereof was gradually raised to room temperature. Then, the reaction mixture was transferred to 100 ml of 1.2N aqueous solution of hydrochloric acid at 5° C. or below, and the organic layer was separated therefrom and the aqueous layer was extracted twice with 100 ml of ethyl acetate. The organic layers were combined and washed with saturated aqueous solution with sodium chloride, dried over anhydrous magnesium sulfate. The resulting organic layer was filtered and the solvent was removed under reduced pressure. Thus obtained concentrate was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 8 g of the desired compound. stored at -60° C This liquid was carefully added dropwise After the resulting liquid was stirred at -60° C. for 2 hours a temperature thereof was gradually raised to room temperature the organic layer was separated the aqueous layer was extracted twice with 100 ml of ethyl acetate washed with saturated aqueous solution with sodium chloride dried over anhydrous magnesium sulfate The resulting organic layer was filtered the solvent was removed under reduced pressure Thus obtained concentrate was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1)

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an atmosphere of argon, 850 ml of THF solution of 2,4-difluorophenylmagnesium bromide prepared from 202.6 g (1.05 mol) of 2,4-difluorobromobenzene and 26.7 g (1.1 mol) of magnesium turnings was added dropwise at -30° C. to 1.7 l of THF solution of 174 g (1.00 mol) of 1,3-diacetoxyacetone which was previously cooled to -30° C. After the resulting liquid was stirred at -60° C. for 2 hours, a temperature thereof was gradually raised to room temperature. Then, to the reaction mixture was added 1 l of 1.2N aqueous solution of hydrochloric acid at 5° C. or below, and an aqueous layer was extracted twice with 1 l of ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium chloride, dried and concentrated under reduced pressure to give 302 g of crude oil. The obtained oil was purified by means of column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 125 g of the desired compound. The compound was recrystallized from toluene/hexane. a temperature thereof was gradually raised to room temperature an aqueous layer was extracted twice with 1 l of ethyl acetate The organic layer was washed with saturated aqueous solution of sodium chloride dried concentrated under reduced pressure to give 302 g of crude oil The obtained oil was purified by means of column chromatography on silica gel (hexane:ethyl acetate=1:1)

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

Procedure: Under an atmosphere of argon, 90 g of 1,3-dihydroxyacetone dimer and 250 mg of 4-(N,N-dimethylamino)pyridine were dissolved in 250 ml of pyridine. To the resulting solution, 225 ml of acetic anhydride was added dropwise at room temperature over 1 hour. After the resulting liquid was stirred at room temperature for 30 minutes, thereto was added 50 ml of methanol and the resulting liquid was further stirred at room temperature for 30 minutes. The solvent was removed under reduced pressure and the residue was subjected to a recrystallization from ether-petroleum ether to give 190 g of the desired compound. the resulting liquid was further stirred at room temperature for 30 minutes The solvent was removed under reduced pressure the residue was subjected to a recrystallization from ether-petroleum ether

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

Procedure: Under an atmosphere of argon, 90 g of 1,3-dihydroxyacetone dimer and 250 mg of 4-(N,N-dimethylamino)pyridine were dissolved in 250 ml of pyridine. To the resulting solution, 225 ml of acetic anhydride was added dropwise at room temperature over 1 hour. After the resulting liquid was stirred at room temperature for 30 minutes, thereto was added 50 ml of methanol and the resulting liquid was further stirred at room temperature for 30 minutes. The solvent was removed under reduced pressure and the residue was subjected to a recrystallization from ether-petroleum ether to give 190 g of the desired compound. the resulting liquid was further stirred at room temperature for 30 minutes The solvent was removed under reduced pressure the residue was subjected to a recrystallization from ether-petroleum ether

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an atmosphere of argon, 22.5 g of 2,4-difluorobromobenzene was dissolved in 200 ml of diethyl ether and to the resulting solution was added dropwise 73 mg of 1.63 M n-hexane solution of n-butyllithium at -30° C. The resulting liquid was stirred for 1 hour and stored at -60° C. This liquid was carefully added dropwise using an injection cylinge to 150 ml of diethyl ether solution of 17.4 g of 1,3-diacetoxyacetone which was previously cooled to -30° C. After the resulting liquid was stirred at -60° C. for 2 hours, a temperature thereof was gradually raised to room temperature. Then, the reaction mixture was transferred to 100 ml of 1.2 N aqueous solution of hydrochloric acid at 5° C. or below, and the organic layer was separated therefrom and the aqueous layer was extracted twice with 100 ml of ethyl acetate. The organic layers were combined and washed with saturated aqueous solution with sodium chloride, dried over anhydrous magnesium sulfate. The resulting organic layer was filtered and the solvent was removed under reduced pressure. Thus obtained concentrate was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 8 g of the desired compound. stored at -60° C This liquid was carefully added dropwise After the resulting liquid was stirred at -60° C. for 2 hours a temperature thereof was gradually raised to room temperature the organic layer was separated the aqueous layer was extracted twice with 100 ml of ethyl acetate washed with saturated aqueous solution with sodium chloride dried over anhydrous magnesium sulfate The resulting organic layer was filtered the solvent was removed under reduced pressure Thus obtained concentrate was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1)

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an atmosphere of argon, 22.5 g of 2,4-difluorobromobenzene was dissolved in 200 ml of diethyl ether and to the resulting solution was added dropwise 73 mg of 1.63 M n-hexane solution of n-butyllithium at -30° C. The resulting liquid was stirred for 1 hour and stored at -60° C. This liquid was carefully added dropwise using an injection cylinge to 150 ml of diethyl ether solution of 17.4 g of 1,3-diacetoxyacetone which was previously cooled to -30° C. After the resulting liquid was stirred at -60° C. for 2 hours, a temperature thereof was gradually raised to room temperature. Then, the reaction mixture was transferred to 100 ml of 1.2 N aqueous solution of hydrochloric acid at 5° C. or below, and the organic layer was separated therefrom and the aqueous layer was extracted twice with 100 ml of ethyl acetate. The organic layers were combined and washed with saturated aqueous solution with sodium chloride, dried over anhydrous magnesium sulfate. The resulting organic layer was filtered and the solvent was removed under reduced pressure. Thus obtained concentrate was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 8 g of the desired compound. stored at -60° C This liquid was carefully added dropwise After the resulting liquid was stirred at -60° C. for 2 hours a temperature thereof was gradually raised to room temperature the organic layer was separated the aqueous layer was extracted twice with 100 ml of ethyl acetate washed with saturated aqueous solution with sodium chloride dried over anhydrous magnesium sulfate The resulting organic layer was filtered the solvent was removed under reduced pressure Thus obtained concentrate was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1)

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an atmosphere of argon, 850 ml of THF solution of 2,4-difluorophenylmagnesium bromide prepared from 202.6 g (1.05 mol) of 2,4-difluorobromobenzene and 26.7 g (1.1 mol) of magnesium turnings was added dropwise at -30° C. to 1.7 l of THF solution of 174 g (1.00 mol) of 1,3-diacetoxyacetone which was previously cooled to -30° C. After the resulting liquid was stirred at -60° C. for 2 hours, a temperature thereof was gradually raised to room temperature. Then, to the reaction mixture was added 1 l of 1.2 N aqueous solution of hydrochloric acid at 5° C. or below, and an aqueous layer was extracted twice with 1 l of ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium chloride, dried and concentrated under reduced pressure to give 302 g of crude oil. The obtained oil was purified by means of column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 125 g of the desired compound. The compound was recrystallized from toluene/hexane a temperature thereof was gradually raised to room temperature an aqueous layer was extracted twice with 1 l of ethyl acetate The organic layer was washed with saturated aqueous solution of sodium chloride dried concentrated under reduced pressure to give 302 g of crude oil The obtained oil was purified by means of column chromatography on silica gel (hexane:ethyl acetate=1:1)