diethyl sulfite

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

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 206.6 g (0.47 mol) of a 35 percent mixture of 4-chloroacetoacetyl chloride in methylene chloride was cooled to -10° C. Under nitrogen, 147.2 g (3.2 mol) of ethanol was added in 30 minutes, and then 83.3 g (0.7 mol) of thionyl chloride was added in 30 minutes (formation of diethyl sulfite). The temperature was raised to 55° to 60° C. in an hour, and then it was stirred for 1 hour more at 55° to 60° C. Then the excess ethanol and methylene chloride was distilled off at reduced pressure. The residue (raw 4-chloro-3,3-diethoxybutanoic acid ester) was mixed with 0.27 g of methanesulfonic acid and warmed at a pressure of 75 mbars to 125° to 130° C. Thus, the formed ethanol and excess diethyl sulfite were distilled off. The residue (raw 4-chloro-3- ethoxy -but-2E-enoic acid ethyl ester) was taken up in 110.2 g (120 ml) of toluene and the organic phase was washed with 69.8 g of aqueous 16 percent HCl for 30 minutes, with 32.1 g of an aqueous 10 percent sodium chloride solution for 10 minutes, with 134 g of aqueous 10 percent NaOH for 75 minutes and finally with 32.1 g of aqueous 10 percent sodium chloride solution for 10 minutes. The toluene was then evaporated off and the residue was distilled at a pressure of 2 mbars and a temperature of 78° to 80° C. 4-chloro-3-ethoxy-but-2E-enoic acid ethyl ester was obtained in a yield of 80.6 g (88.5 percent) in a purity of 99.8 percent (GC). The temperature was raised to 55° to 60° C. in an hour Then the excess ethanol and methylene chloride was distilled off at reduced pressure The residue (raw 4-chloro-3,3-diethoxybutanoic acid ester) was mixed with 0.27 g of methanesulfonic acid Thus, the formed ethanol and excess diethyl sulfite were distilled off the organic phase was washed with 69.8 g of aqueous 16 percent HCl for 30 minutes, with 32.1 g of an aqueous 10 percent sodium chloride solution for 10 minutes, with 134 g of aqueous 10 percent NaOH for 75 minutes and finally with 32.1 g of aqueous 10 percent sodium chloride solution for 10 minutes The toluene was then evaporated off the residue was distilled at a pressure of 2 mbars a temperature of 78° to 80° C

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

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

Procedure: In a 50 ml round bottom flask equipped with a reflux condenser, a magnetic stirrer and an inert gas supply, 1.91 g (10.0 mmol) (3R,4S,5R)-5-amino-3,4-dihydroxy-cyclohex-1-enecarboxylic acid mono hydrate was suspended with 19 ml ethanol and cooled to 0-5° C., treated slowly (3 min) with 0.80 ml (11.0 mmol) thionyl chloride, then 1.28 ml (10.0 mmol) diethyl sulfite was added, the mixture was heated to reflux for 3 hours (a gas mixture was evolved), the black reaction mixture was cooled to 20-25° C., to the black suspension, 19 ml ethyl acetate was added dropwise in the course of 30 min, then the mixture was cooled to 0-5° C. and stirred for 1 hour at 0-5° C. The black suspension was filtered, the filter cake was washed portion wise with a mixture of 6.5 ml ethanol and 6.5 ml ethylacetate. The light grey crystals were dried at 40° C./10 mbar/1 h, to obtain 1.57 g (3R,4S,5R)-5-amino-3,4-dihydroxy-cyclohex-1-enecarboxylic acid ethyl ester hydrochloride, as light grey crystals. In a 50 ml round bottom flask equipped with a reflux condenser, a magnetic stirrer the mixture was heated to reflux for 3 hours (a gas mixture was added dropwise in the course of 30 min the mixture was cooled to 0-5° C. The black suspension was filtered the filter cake was washed portion wise with a mixture of 6.5 ml ethanol and 6.5 ml ethylacetate The light grey crystals were dried at 40° C./10 mbar/1 h

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

Procedure: 200 mmol of 1-methylpyrrolidone (Aldrich) in solution in 100 ml of toluene were quaternized with 100 mmol of diethyl sulfite (Aldrich), added slowly at 0° C., with stirring for 24 hours at ambient temperature. After evaporation of the solvent and drying, N-methyl-N-propylpyrrolidinium ethylsulfamate was obtained. 50 mmol of ethylsulfamate were solubilized in 50 ml of acetonitrile, and were reacted with 50 mmol of KBFFST. After stirring for 2 hours, and then filtration, evaporation of the solvent and drying, the N-propane-N-methylpyrrolidinium salt of 3,5-difluorosulfonyl-1,2,4-triazole (PYR13BFST) corresponding to the following formula was obtained: added slowly at 0° C. After evaporation of the solvent drying

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

Procedure: 5-Chloro-2-hydroxynicotinic acid [11.95 g; Synthetic Comm. (1989), 19, 553] was suspended in thionyl chloride (52 mL) and anhydrous dimethylformamide (2 mL) was added. The suspension was refluxed 3 h, then concentrated under a nitrogen stream to remove the bulk of excess thionyl chloride before adding anhydrous ethanol (30 mL) giving a mixture of the desired ester and diethyl sulfite. The resulting mixture was concentrated in vacuo to remove the ethanol yielding a suspension. The solids were then filtered off and washed with anhydrous diethyl ether (2×10 mL). The combined filtrates were concentrated in vacuo yielding crude product. Purification by silica gel chromatography (ethyl acetate:hexanes 8:92) gave pure title compound (4.75 g). The suspension was refluxed 3 h concentrated under a nitrogen to remove the bulk of excess thionyl chloride before adding anhydrous ethanol (30 mL) giving The resulting mixture was concentrated in vacuo to remove the ethanol yielding a suspension The solids were then filtered off washed with anhydrous diethyl ether (2×10 mL) The combined filtrates were concentrated in vacuo yielding crude product Purification by silica gel chromatography (ethyl acetate:hexanes 8:92)

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

Procedure: 2.8 g of 1-(m-nitrophenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione was dissolved in 30 ml of dry dimethylformamide. To the solution was added 0.6 g of about 50 % sodium hydride, and stirring was performed for 30 minutes. To the mixture was further added 3.5 g of diethylsulfite and the whole was reacted for 2 hours at room temperature. After the reaction was finished, the solvent was distilled off from the mixture under reduced pressure. To the residue thus obtained was added water to precipitate a crude product. This product was recrystallized from methanol to yield 2.7 g of 1-(m-nitrophenyl)-3-ethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione as pale yellow prisms, melting at 210°-211°C. the whole was reacted for 2 hours at room temperature the solvent was distilled off from the mixture under reduced pressure To the residue thus obtained to precipitate a crude product This product was recrystallized from methanol

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 206.6 g (0.47 mol) of a 35 percent mixture of 4-chloroacetoacetyl chloride in methylene chloride was cooled to -10° C. Under nitrogen, 147.2 g (3.2 mol) of ethanol was added in 30 minutes, and then 83.3 g (0.7 mol) of thionyl chloride was added in 30 minutes (formation of diethyl sulfite). The temperature was raised to 55° to 60° C. in an hour, and then it was stirred for 1 hour more at 55° to 60° C. Then the excess ethanol and methylene chloride was distilled off at reduced pressure. The residue (raw 4-chloro-3,3-diethoxybutanoic acid ester) was mixed with 0.27 g of methanesulfonic acid and warmed at a pressure of 75 mbars to 125° to 130° C. Thus, the formed ethanol and excess diethyl sulfite were distilled off. The residue (raw 4-chloro-3- ethoxy -but-2E-enoic acid ethyl ester) was taken up in 110.2 g (120 ml) of toluene and the organic phase was washed with 69.8 g of aqueous 16 percent HCl for 30 minutes, with 32.1 g of an aqueous 10 percent sodium chloride solution for 10 minutes, with 134 g of aqueous 10 percent NaOH for 75 minutes and finally with 32.1 g of aqueous 10 percent sodium chloride solution for 10 minutes. The toluene was then evaporated off and the residue was distilled at a pressure of 2 mbars and a temperature of 78° to 80° C. 4-chloro-3-ethoxy-but-2E-enoic acid ethyl ester was obtained in a yield of 80.6 g (88.5 percent) in a purity of 99.8 percent (GC). The temperature was raised to 55° to 60° C. in an hour Then the excess ethanol and methylene chloride was distilled off at reduced pressure The residue (raw 4-chloro-3,3-diethoxybutanoic acid ester) was mixed with 0.27 g of methanesulfonic acid Thus, the formed ethanol and excess diethyl sulfite were distilled off the organic phase was washed with 69.8 g of aqueous 16 percent HCl for 30 minutes, with 32.1 g of an aqueous 10 percent sodium chloride solution for 10 minutes, with 134 g of aqueous 10 percent NaOH for 75 minutes and finally with 32.1 g of aqueous 10 percent sodium chloride solution for 10 minutes The toluene was then evaporated off the residue was distilled at a pressure of 2 mbars a temperature of 78° to 80° C