dimethyl 2-fluoropropanedioate

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

Procedure: 48 g (0.48 mol) of potassium bicarbonate were dissolved in 535 g (6.59 mol) of aqueous formaldehyde solution (37% strength by weight) in a 4-liter glass flask. 841 g (5.6 mol) of dimethyl α-fluoromalonate were added dropwise to this solution., with stirring, in the course of 31/2 hours; the temperature was kept meanwhile within the range from 20° to 25° C. Stirring was continued for 2 hours at the same temperature, and during this time dimethyl α-hydroxymethyl-α-fluoromalonate was precipitated in the form of a colorless solid. 2,500 g of an aqueous, saturated solution of ammonium sulfate were then added to the reaction mixture, which was then extracted with methylene dichloride. The extraction solution was dried by means of anhydrous sodium sulfate. 906 g (90% of theory) of dimethyl a-hydroxymethyl-α-fluoromalonate were obtained after removing the methylene dichloride by distillation (bath temperature 40° C., 25 mbar). was kept meanwhile within the range from 20° to 25° C during this time dimethyl α-hydroxymethyl-α-fluoromalonate was precipitated in the form of a colorless solid 2,500 g of an aqueous, saturated solution of ammonium sulfate were then added to the reaction mixture, which was then extracted with methylene dichloride The extraction solution was dried by means of anhydrous sodium sulfate

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

Procedure: 48 g (0.48 mol) of potassium bicarbonate were dissolved in 535 g (6.59 mol) of aqueous formaldehyde solution (37% strength by weight) in a 4-liter glass flask. 841 g (5.6 mol) of dimethyl α-fluoromalonate were added dropwise to this solution., with stirring, in the course of 31/2 hours; the temperature was kept meanwhile within the range from 20° to 25° C. Stirring was continued for 2 hours at the same temperature, and during this time dimethyl α-hydroxymethyl-α-fluoromalonate was precipitated in the form of a colorless solid. 2,500 g of an aqueous, saturated solution of ammonium sulfate were then added to the reaction mixture, which was then extracted with methylene dichloride. The extraction solution was dried by means of anhydrous sodium sulfate. 906 g (90% of theory) of dimethyl a-hydroxymethyl-α-fluoromalonate were obtained after removing the methylene dichloride by distillation (bath temperature 40° C., 25 mbar). was kept meanwhile within the range from 20° to 25° C during this time dimethyl α-hydroxymethyl-α-fluoromalonate was precipitated in the form of a colorless solid 2,500 g of an aqueous, saturated solution of ammonium sulfate were then added to the reaction mixture, which was then extracted with methylene dichloride The extraction solution was dried by means of anhydrous sodium sulfate

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

Procedure: In the first process stage, dimethyl α-fluoromalonate is subjected to hydroxymethylation with formaldehyde. (Dimethyl α-fluoromalonate is a known compound; see Journal of Fluorine Chemistry 25 (1984), 203-212.) The formaldehyde is preferably employed in the form of an aqueous solution having a formaldehyde content of 30 to 40% by weight. The formaldehyde is employed in an amount of 1 to 10 mot, preferably 1.1 to 3 mot (relative to 1 mol of dimethyl α-fluoromalonate). It is also possible to use paraformaldehyde, hexamethylenetetramine or 1,3,5-trioxane instead of formaldehyde. It is advantagous to carry out the reaction in the presence of a basic catalyst, which is then used in an amount of 2 to 50, preferably 5 to 15, mol % (relative to the dimethyl α-fluoromalonate). The catalyst used is, in particular, an alkali metal bicarbonate, for example potassium bicarbonate and sodium bicarbonate. The reaction is carried out at a temperature of 5° to 40° C., preferably 15° to 30° C. The dimethyl α -hydroxymethyl-α-fluoromalonate formed is then isolated from the reaction mixture, preferably by salting out or extraction by means of a water-immiscible organic solvent. A suitable solvent is, above all, an aliphatic chlorinated hydrocarbon having 1 to 4 carbon atoms, for example methylene dichloride, chloroform, carbon tetrachloride, 1,1-dichloroethane or 1,2-dichloroethane. A combination of salting out and extraction is particularly advantageous; a saturated salt solution (ammonium sulfate or sodium chloride) is then first added to the reaction mixture, and this mixture is then extracted. Dimethyl α-hydroxymethyl-α-fluoromalonate is obtained in the form of a colorless solid by evaporating the solvent. the reaction in the presence of a basic catalyst, which is carried out at a temperature of 5° to 40° C., preferably 15° to 30° C

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

Procedure: In the first process stage, dimethyl α-fluoromalonate is subjected to hydroxymethylation with formaldehyde. (Dimethyl α-fluoromalonate is a known compound; see Journal of Fluorine Chemistry 25 (1984), 203-212.) The formaldehyde is preferably employed in the form of an aqueous solution having a formaldehyde content of 30 to 40% by weight. The formaldehyde is employed in an amount of 1 to 10 mot, preferably 1.1 to 3 mot (relative to 1 mol of dimethyl α-fluoromalonate). It is also possible to use paraformaldehyde, hexamethylenetetramine or 1,3,5-trioxane instead of formaldehyde. It is advantagous to carry out the reaction in the presence of a basic catalyst, which is then used in an amount of 2 to 50, preferably 5 to 15, mol % (relative to the dimethyl α-fluoromalonate). The catalyst used is, in particular, an alkali metal bicarbonate, for example potassium bicarbonate and sodium bicarbonate. The reaction is carried out at a temperature of 5° to 40° C., preferably 15° to 30° C. The dimethyl α -hydroxymethyl-α-fluoromalonate formed is then isolated from the reaction mixture, preferably by salting out or extraction by means of a water-immiscible organic solvent. A suitable solvent is, above all, an aliphatic chlorinated hydrocarbon having 1 to 4 carbon atoms, for example methylene dichloride, chloroform, carbon tetrachloride, 1,1-dichloroethane or 1,2-dichloroethane. A combination of salting out and extraction is particularly advantageous; a saturated salt solution (ammonium sulfate or sodium chloride) is then first added to the reaction mixture, and this mixture is then extracted. Dimethyl α-hydroxymethyl-α-fluoromalonate is obtained in the form of a colorless solid by evaporating the solvent. the reaction in the presence of a basic catalyst, which is carried out at a temperature of 5° to 40° C., preferably 15° to 30° C

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

Procedure: The process according to the invention is carried out in three stages: dimethyl α-fluoromalonate is first reacted with formaldehyde to give dimethyl α-hydroxymethyl-α-fluoromalonate, the latter is then hydrolyzed and the hydrolysis product is decarboxylated and dehydrated, and finally, the resuiting α-fluoroacrylic acid is esterified with a substituted phenol.

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

Procedure: The process according to the invention is carried out in three stages: dimethyl α-fluoromalonate is first reacted with formaldehyde to give dimethyl α-hydroxymethyl-α-fluoromalonate, the latter is then hydrolyzed and the hydrolysis product is decarboxylated and dehydrated, and finally, the resuiting α-fluoroacrylic acid is esterified with a substituted phenol.

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

Procedure: A 3-neck, 5-L round-bottom flask equipped with a vacuum distillation head, a thermometer, and a magnetic stir bar was charged with dimethyl fluoromalonate (339 g assayed at 83% purity by VPC, 1.88 mol), benzyl alcohol (935 mL, 9.04 mol), toluene (846 mL), and p-toluenesulfonic acid monohydrate (21.5 g, 0.113 mol). The mixture was heated under vacuum (10-15 inches of Hg) until all of the toluene had distilled, then at 28-29 inches of Hg (water aspirator vacuum), the reaction temperature being maintained at 100° to 115° C. The progress of the reaction was monitored by 19F NMR. After a total of 7 hours, the heat was removed, and the mixture was allowed to cool, with continued stirring. When the temperature had lowered to 75° C., isopropanol (450 mL) was added. When the temperature had lowered to 55° C., hexane (1 L) was added. The product crystallized out and the mixture was placed in the freezer overnight. The product was filtered, washed with hexane (2xl L), sucked dry, and dried overnight in vacuo. The yield was 452 g (96% pure by weight). A second crop of 29 g was obtained from the combined filtrates and washings, for a total yield of 81%. had distilled at 28-29 inches of Hg (water aspirator vacuum), the reaction temperature being maintained at 100° to 115° C After a total of 7 hours, the heat was removed to cool, with continued stirring had lowered to 75° C. isopropanol (450 mL) was added had lowered to 55° C. hexane (1 L) was added The product crystallized out was placed in the freezer overnight The product was filtered washed with hexane (2xl L) sucked dry dried overnight in vacuo A second crop of 29 g was obtained from the combined filtrates and washings, for a total yield of 81%

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

Procedure: A 3-neck, 5-L round-bottom flask equipped with a vacuum distillation head, a thermometer, and a magnetic stir bar was charged with dimethyl fluoromalonate (339 g assayed at 83% purity by VPC, 1.88 mol), benzyl alcohol (935 mL, 9.04 mol), toluene (846 mL), and p-toluenesulfonic acid monohydrate (21.5 g, 0.113 mol). The mixture was heated under vacuum (10-15 inches of Hg) until all of the toluene had distilled, then at 28-29 inches of Hg (water aspirator vacuum), the reaction temperature being maintained at 100° to 115° C. The progress of the reaction was monitored by 19F NMR. After a total of 7 hours, the heat was removed, and the mixture was allowed to cool, with continued stirring. When the temperature had lowered to 75° C., isopropanol (450 mL) was added. When the temperature had lowered to 55° C., hexane (1 L) was added. The product crystallized out and the mixture was placed in the freezer overnight. The product was filtered, washed with hexane (2xl L), sucked dry, and dried overnight in vacuo. The yield was 452 g (96% pure by weight). A second crop of 29 g was obtained from the combined filtrates and washings, for a total yield of 81%. had distilled at 28-29 inches of Hg (water aspirator vacuum), the reaction temperature being maintained at 100° to 115° C After a total of 7 hours, the heat was removed to cool, with continued stirring had lowered to 75° C. isopropanol (450 mL) was added had lowered to 55° C. hexane (1 L) was added The product crystallized out was placed in the freezer overnight The product was filtered washed with hexane (2xl L) sucked dry dried overnight in vacuo A second crop of 29 g was obtained from the combined filtrates and washings, for a total yield of 81%

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

Procedure: In the first process step, dimethyl α-fluoromalonate is subjected to a hydroxymethylation with formaldehyde. (Dimethyl α-fluoromalonate is a known compound; see Journal of Fluorine Chemistry 25 (1984), 203-212.) The formaldehyde is preferably used in the form of an aqueous solution which has a formaldehyde content of 30 to 40 percent by weight. The formaldehyde is used in an amount of 1 to 10 moles, preferably 1.1 to 3 moles (based on 1 mole of dimethyl o,-fluoromalonate). Instead of formaldehyde, it is also possible to use paraformaldehyde, hexamethylenetetramine or 1,3,5-trioxane. It is advantageous to carry out the reaction in the presence of a basic catalyst which is then used in an amount of 2 to 50, preferably 5 to 15, mol % (based on dimethyl α-fluoromalonate). The catalyst used is in particular an alkali metal hydrogencarbonate, for example potassium hydrogencarbonate and sodium hydrogencarbonate. The reaction is carried out at a temperature of 5° to 40° C., preferably of 15 ° to 30° C. The resulting dimethyl ester of α-hydroxymethyl-α-fluoromalonic acid is then isolated out of the reaction mixture, preferably by salting out or extraction by means of a water-nonmiscible organic solvent. A suitable solvent is in particular an aliphatic chlorohydrocarbon having 1 to 4 carbon atoms, for example dichloromethane, trichloromethane, tetrarhloromethane, 1,1-dichloroethane, 1,2-dichloroethane. A combination of salting out and extraction is particularly advantageous; therein the reaction mixture has first added to it a saturated salt solution (ammonium sulfate, sodium chloride), and this mixture is then extracted. By evaporating the solvent, α-hydroxymethyl-α-fluoromalonic acid is obtained as a colorless solid. the reaction in the presence of a basic catalyst which is carried out at a temperature of 5° to 40° C., preferably of 15 ° to 30° C

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

Procedure: The process according to the invention for preparing an α-fluoroacrylic acid ester is carried out in three stages. First dimethyl α-fluoromalonate is reacted with formaldehyde to give dimethyl a-hydroxymethyl-α-fluoromalonate, which is then hydrolyzed and the hydrolysis product is dicarboxylated and dehydrated, and finally the resulting α-fluoroacrylic acid is esterified with an alcohol of the formula (3).

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

Procedure: 48 g (0.48 mol) of potassium bicarbonate were dissolved in 535 g (6.59 mol) of aqueous formaldehyde solution (37% strength by weight) in a 4-liter glass flask. 841 g (5.6 mol) of dimethyl α-fluoromalonate were added dropwise to this solution., with stirring, in the course of 31/2 hours; the temperature was kept meanwhile within the range from 20° to 25° C. Stirring was continued for 2 hours at the same temperature, and during this time dimethyl α-hydroxymethyl-α-fluoromalonate was precipitated in the form of a colorless solid. 2,500 g of an aqueous, saturated solution of ammonium sulfate were then added to the reaction mixture, which was then extracted with methylene dichloride. The extraction solution was dried by means of anhydrous sodium sulfate. 906 g (90% of theory) of dimethyl a-hydroxymethyl-α-fluoromalonate were obtained after removing the methylene dichloride by distillation (bath temperature 40° C., 25 mbar). was kept meanwhile within the range from 20° to 25° C during this time dimethyl α-hydroxymethyl-α-fluoromalonate was precipitated in the form of a colorless solid 2,500 g of an aqueous, saturated solution of ammonium sulfate were then added to the reaction mixture, which was then extracted with methylene dichloride The extraction solution was dried by means of anhydrous sodium sulfate

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

Procedure: In the first process stage, dimethyl α-fluoromalonate is subjected to hydroxymethylation with formaldehyde. (Dimethyl α-fluoromalonate is a known compound; see Journal of Fluorine Chemistry 25 (1984), 203-212.) The formaldehyde is preferably employed in the form of an aqueous solution having a formaldehyde content of 30 to 40% by weight. The formaldehyde is employed in an amount of 1 to 10 mot, preferably 1.1 to 3 mot (relative to 1 mol of dimethyl α-fluoromalonate). It is also possible to use paraformaldehyde, hexamethylenetetramine or 1,3,5-trioxane instead of formaldehyde. It is advantagous to carry out the reaction in the presence of a basic catalyst, which is then used in an amount of 2 to 50, preferably 5 to 15, mol % (relative to the dimethyl α-fluoromalonate). The catalyst used is, in particular, an alkali metal bicarbonate, for example potassium bicarbonate and sodium bicarbonate. The reaction is carried out at a temperature of 5° to 40° C., preferably 15° to 30° C. The dimethyl α -hydroxymethyl-α-fluoromalonate formed is then isolated from the reaction mixture, preferably by salting out or extraction by means of a water-immiscible organic solvent. A suitable solvent is, above all, an aliphatic chlorinated hydrocarbon having 1 to 4 carbon atoms, for example methylene dichloride, chloroform, carbon tetrachloride, 1,1-dichloroethane or 1,2-dichloroethane. A combination of salting out and extraction is particularly advantageous; a saturated salt solution (ammonium sulfate or sodium chloride) is then first added to the reaction mixture, and this mixture is then extracted. Dimethyl α-hydroxymethyl-α-fluoromalonate is obtained in the form of a colorless solid by evaporating the solvent. the reaction in the presence of a basic catalyst, which is carried out at a temperature of 5° to 40° C., preferably 15° to 30° C