ethyl 4,4,4-trifluoro-3-hydroxybutanoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 4,4,4-trifluoroacetoacetate (50 g), under a blanket of nitrogen gas, is heated to 40° C. and treated with platinum (0.1 g of 5% Pt/alumina, 0.01% load) and triethylamine (0.2 g, 0.4% load). Hydrogen is charged to a pressure of 5 bars, and the mixture agitated at 40° C. for 6h. After filtration to remove the catalyst, 48.5 g (96% yield) of ethyl 4,4,4-trifluoro-3-hydroxybutyrate is obtained. After filtration to remove the catalyst

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 4,4,4-trifluoroacetoacetate (50 g), under a blanket of nitrogen gas, is heated to 40° C. and treated with platinum (0.5 g of 1% Pt/C, 0.05% load) and triethylamine (0.2 g, 0.4% load). Hydrogen is charged to a pressure of 5 bars, and the mixture agitated at 40° C. for 6h. After filtration to remove the catalyst, 48.5 g (96% yield) of ethyl 4,4,4-trifluoro-3-hydroxybutyrate is obtained. After filtration to remove the catalyst

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 4,4,4-trifluoroacetoacetate (50 g), under a blanket of nitrogen gas, is heated to 40° C. and treated with platinum (0.1 g of 5% Pt/C, 0.01% load) and methanesulfonic acid (1.5 g, 2.9% load). Hydrogen is charged to a pressure of 5 bars, and the mixture agitated at 40° C. for 6h. After filtration to remove the catalyst, 25.3 g (50% yield) of ethyl 4,4,4-trifluoro-3-hydroxybutyrate is obtained. After filtration to remove the catalyst

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 4,4,4-trifluoroacetoacetate (50 g), under a blanket of nitrogen gas, was heated to 40° C. and treated with platinum (0.1 g of 5% Pt/C, 0.01% load) and triethylamine (1.5 g, 2.9% load). Hydrogen was charged to a pressure of 5 bars, and the mixture agitated at 40° C. for 6h. After filtration to remove the catalyst, 48.5 g (96% yield) of ethyl 4,4,4-trifluoro-3-hydroxybutyrate was obtained. After filtration to remove the catalyst

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 4,4,4-trifluoroacetoacetate (350 g), under a blanket of nitrogen gas, was heated to 40° C. and treated with platinum (0.7 g of 5% Pt/C, 0.01% load) and triethylamine (1.5 g, 0.4% load). Hydrogen was charged to a pressure of 5 bars and the mixture agitated at 40° C. for 6h. After filtration to remove the catalyst, 341 g (96% yield) of ethyl 4,4,4-trifluoro-3-hydroxybutyrate was obtained. After filtration to remove the catalyst

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

実験手順: There are a number of ways of reducing β-ketoesters which have been disclosed. In addition to hydrogenation, reduction with zinc/acetic acid or with borohydride reagents are known. For the hydrogenation reactions reported in the literature, most use ruthenium, nickel, or baker's yeast as catalyst. All use a solvent. F. G. Kathawala et al. in Helvetica Chimica Acta, 69, 803-805 (1986) disclose an example in which 5% platinum on carbon is used as a catalyst for the reduction of various β-ketoesters using methanol as a solvent. T. Fujima et al. in JP 09268146 A2, Oct. 14, 1997 disclose the hydrogenation of ethyl trifluoroacetoacetate using a nickel catalyst in tetrahydrofuran solvent to provide ethyl 4,4,4-trifluoro-3-hydroxybutyrate in 78% yield. N. Sayo et al. in U.S. 4,933,482, Jun. 12, 1990 disclose the hydrogenation of ethyl trifluoroacetoacetate using a ruthenium catalyst in a polar solvent such as an alcohol or tetrahydrofuran to provide ethyl 4,4,4-trifluoro-3-hydroxybutyrate in 95% yield. None of these references disclose or suggest the process of the present invention in which we have discovered that no solvent is necessary for the catalytic hydrogenation.

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

実験手順: There are a number of ways of reducing β-ketoesters which have been disclosed. In addition to hydrogenation, reduction with zinc/acetic acid or with borohydride reagents are known. For the hydrogenation reactions reported in the literature, most use ruthenium, nickel, or baker's yeast as catalyst. All use a solvent. F. G. Kathawala et al. in Helvetica Chimica Acta, 69, 803-805 (1986) disclose an example in which 5% platinum on carbon is used as a catalyst for the reduction of various β-ketoesters using methanol as a solvent. T. Fujima et al. in JP 09268146 A2, Oct. 14, 1997 disclose the hydrogenation of ethyl trifluoroacetoacetate using a nickel catalyst in tetrahydrofuran solvent to provide ethyl 4,4,4-trifluoro-3-hydroxybutyrate in 78% yield. N. Sayo et al. in U.S. 4,933,482, Jun. 12, 1990 disclose the hydrogenation of ethyl trifluoroacetoacetate using a ruthenium catalyst in a polar solvent such as an alcohol or tetrahydrofuran to provide ethyl 4,4,4-trifluoro-3-hydroxybutyrate in 95% yield. None of these references disclose or suggest the process of the present invention in which we have discovered that no solvent is necessary for the catalytic hydrogenation.

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of 19.31 g of ethyl trifluoroacetoacetate (Fairfield Chemical) in 50 ml of ethyl acetate was hydrogenated at atmospheres on a Parr shaker over (0.5 g) PtO2 as a catalyst. The volatiles were removed and the residue distilled under high vacuum to afford 14.75 g (76%) of the title compound as a low melting solid. bp=47°-49° C. at 0.1 mm of Hg, mp (uncorrected)=about 25° C. The volatiles were removed the residue distilled under high vacuum

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

実験手順: To a suspension of 91.2 g (2.4 mol) of sodium borohydride in 6 l of CH2Cl2 cooled at +2° C., are dropwise added 1473 g of ethyl 4,4,4-trifluoroacetoacetate while keeping temperature between +4° and +7° C. After the introduction, 100 ml of absolute ethanol are added while keeping temperature at +3° C. The reaction medium is washed with bicarbonated water. The organic phase is concentrated and the product is distilled at 78° C. under 10 mm Hg. cooled at +2° C. temperature between +4° and +7° C at +3° C The reaction medium is washed with bicarbonated water The organic phase is concentrated the product is distilled at 78° C. under 10 mm Hg

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

実験手順: To a suspension of 91.2 g (2.4 mol) of sodium borohydride in 6 l of CH2Cl2 cooled at +2° C., are dropwise added 1473 g of ethyl 4,4,4-trifluoroacetoacetate while keeping temperature between +4° and +7° C. After the introduction, 100 ml of absolute ethanol are added while keeping temperature at +3° C. The reaction medium is washed with bicarbonated water. The organic phase is concentrated and the product is distilled at 78° C. under 10 mm Hg. cooled at +2° C. temperature between +4° and +7° C at +3° C The reaction medium is washed with bicarbonated water The organic phase is concentrated the product is distilled at 78° C. under 10 mm Hg