ethyl 6,6,6-trifluoro-3-oxohexanoate

Conditions: temp:37.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 98.8 g of the ethyl 4,4,4-trifluorobutyrylacetate thus obtained was added to 250 ml of a 10% sodium hydroxide solution and vigorously stirred for 12 hours. The pH value of the reaction solution was brought 7.5 with a 10% aqueous sulfuric acid solution. Then 250 ml of toluene, 2.86 g of sodium hydrogencarbonate and 6.43 g of hydrosulfite were added to the solution under an atmosphere of nitrogen and warmed to 37° C. 90 g of methyl glyoxal was added over 1 hour and allowed to react for 12 hours. After 50 g of sodium chloride was added to the solution, the mixture was extracted three times with ethyl acetate. The ethyl acetate layers were combined and dried over anhydrous magnesium sulfate. After removal of the drying agent, the solvent was removed under reduced pressure. The obtained residue was mixed with 450 ml of 5% sodium hydroxide solution and vigorously stirred under ice-water cooling. The pH of the solution was adjusted to 7.3 with a 10% hydrochloric acid solution and then extracted three times with ethyl acetate. The ethyl acetate layer was combined and dried over anhydrous magnesium sulfate. After removal of the drying agent, the solvent was removed under reduced pressure. The obtained residue was distilled under reduced pressure to afford 45 g of the desired (RS)-2-methyl-3-(2,2,2-trifluoroethyl)-4-oxocyclopent-2-en-1-ol in a yield 50%. to react for 12 hours the mixture was extracted three times with ethyl acetate dried over anhydrous magnesium sulfate After removal of the drying agent the solvent was removed under reduced pressure The obtained residue was mixed with 450 ml of 5% sodium hydroxide solution vigorously stirred under ice-water cooling extracted three times with ethyl acetate dried over anhydrous magnesium sulfate After removal of the drying agent the solvent was removed under reduced pressure The obtained residue was distilled under reduced pressure

Conditions: temp:37.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 98.8 g of the ethyl 4,4,4-trifluorobutyrylacetate thus obtained was added to 250 ml of a 10% sodium hydroxide solution and vigorously stirred for 12 hours. The pH value of the reaction solution was brought 7.5 with a 10% aqueous sulfuric acid solution. Then 250 ml of toluene, 2.86 g of sodium hydrogencarbonate and 6.43 g of hydrosulfite were added to the solution under an atmosphere of nitrogen and warmed to 37° C. 90 g of methyl glyoxal was added over 1 hour and allowed to react for 12 hours. After 50 g of sodium chloride was added to the solution, the mixture was extracted three times with ethyl acetate. The ethyl acetate layers were combined and dried over anhydrous magnesium sulfate. After removal of the drying agent, the solvent was removed under reduced pressure. The obtained residue was mixed with 450 ml of 5% sodium hydroxide solution and vigorously stirred under ice-water cooling. The pH of the solution was adjusted to 7.3 with a 10% hydrochloric acid solution and then extracted three times with ethyl acetate. The ethyl acetate layer was combined and dried over anhydrous magnesium sulfate. After removal of the drying agent, the solvent was removed under reduced pressure. The obtained residue was distilled under reduced pressure to afford 45 g of the desired (RS)-2-methyl-3-(2,2,2-trifluoroethyl)-4-oxocyclopent-2-en-1-ol in a yield 50%. to react for 12 hours the mixture was extracted three times with ethyl acetate dried over anhydrous magnesium sulfate After removal of the drying agent the solvent was removed under reduced pressure The obtained residue was mixed with 450 ml of 5% sodium hydroxide solution vigorously stirred under ice-water cooling extracted three times with ethyl acetate dried over anhydrous magnesium sulfate After removal of the drying agent the solvent was removed under reduced pressure The obtained residue was distilled under reduced pressure

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

Procedure: A mixture of 179 g of the 4,4,4-trifluorobutyrylmalonic acid ditheyl ester thus obtained, 260 ml of water and 322 mg of p-toluenesulfonic acid was refluxed with vigorous stirring for 6 hours. The reaction solution was then poured into saturated aqueous sodium hydrogencarbonate solution and extracted three times with diethyl ether. The ether layers were combined and the combined layer was washed with brine, dried over anhydrous magnesium sulfate. After the drying agent was removed, the solvent was removed under reduced pressure. The obtained residue was distilled inder reduced pressure to yield 98.8 g of the desired ethyl 4,4,4-trifluorobutyrylacetate in a yield of 74%. thus obtained extracted three times with diethyl ether the combined layer was washed with brine dried over anhydrous magnesium sulfate After the drying agent was removed the solvent was removed under reduced pressure The obtained residue was distilled inder reduced pressure

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

Procedure: To a stirred solution of Meldrum's Acid (3.0 g, 20.8 mmol) in 100 mL of CH2Cl2, 4-trifluoromethyl butyric acid (2.96 g, 20.8 mmol) was added followed by DMAP (5.08 g, 41.6 mmol) and finally DCC (4.30 g, 20.8 mmol). The reaction stirred overnight at room temperature. The mixture was then filtered and the filtrate washed with 1M HCl, H2O and Brine. The organics were then dried over sodium sulfate, filtered and concentrated to a yellow oil. The material was then dissolved in 100 mL of EtOH and refluxed overnight. The reaction mixture was concentrated and purified by column chromatography (ethyl acetate/hexanes (1:4)) to yield 1.88 g (43%) of a clear oil.: 1H NMR (CDCl3, 400 MHz) δ 4.24–4.10 (q, 2H, J=7.14), 3.45 (s, 2H), 2.93–2.73 (t, 2H, J=7.88), 2.52–2.28 (m, 2H), 1.31–1.20 (t, 3H, J=7.14) The mixture was then filtered the filtrate washed with 1M HCl, H2O and Brine The organics were then dried over sodium sulfate filtered concentrated to a yellow oil The material was then dissolved in 100 mL of EtOH refluxed overnight The reaction mixture was concentrated purified by column chromatography (ethyl acetate/hexanes (1:4))

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

Procedure: To a stirred solution of Meldrum's Acid (3.0 g, 20.8 mmol) in 100 mL of CH2Cl2, 4-trifluoromethyl butyric acid (2.96 g, 20.8 mmol) was added followed by DMAP (5.08 g, 41.6 mmol) and finally DCC (4.30 g, 20.8 mmol). The reaction stirred overnight at room temperature. The mixture was then filtered and the filtrate washed with 1M HCl, H2O and Brine. The organics were then dried over sodium sulfate, filtered and concentrated to a yellow oil. The material was then dissolved in 100 mL of EtOH and refluxed overnight. The reaction mixture was concentrated and purified by column chromatography (ethyl acetate/hexanes (1:4)) to yield 1.88 g (43%) of a clear oil.: 1H NMR (CDCl3, 400 MHz) δ 4.24–4.10 (q, 2H, J=7.14), 3.45 (s, 2H), 2.93–2.73 (t, 2H, J=7.88), 2.52–2.28 (m, 2H), 1.31–1.20 (t, 3H, J=7.14) The mixture was then filtered the filtrate washed with 1M HCl, H2O and Brine The organics were then dried over sodium sulfate filtered concentrated to a yellow oil The material was then dissolved in 100 mL of EtOH refluxed overnight The reaction mixture was concentrated purified by column chromatography (ethyl acetate/hexanes (1:4))

Conditions: temp:37.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 98.8 g of the ethyl 4,4,4-trifluorobutyrylacetate thus obtained was added to 250 ml of a 10% sodium hydroxide solution and vigorously stirred for 12 hours. The pH value of the reaction solution was brought 7.5 with a 10% aqueous sulfuric acid solution. Then 250 ml of toluene, 2.86 g of sodium hydrogencarbonate and 6.43 g of hydrosulfite were added to the solution under an atmosphere of nitrogen and warmed to 37° C. 90 g of methyl glyoxal was added over 1 hour and allowed to react for 12 hours. After 50 g of sodium chloride was added to the solution, the mixture was extracted three times with ethyl acetate. The ethyl acetate layers were combined and dried over anhydrous magnesium sulfate. After removal of the drying agent, the solvent was removed under reduced pressure. The obtained residue was mixed with 450 ml of 5% sodium hydroxide solution and vigorously stirred under ice-water cooling. The pH of the solution was adjusted to 7.3 with a 10% hydrochloric acid solution and then extracted three times with ethyl acetate. The ethyl acetate layer was combined and dried over anhydrous magnesium sulfate. After removal of the drying agent, the solvent was removed under reduced pressure. The obtained residue was distilled under reduced pressure to afford 45 g of the desired (RS)-2-methyl-3-(2,2,2-trifluoroethyl)-4-oxocyclopent-2-en-1-ol in a yield of 50%. (b.p. 100°-133° C., 0.52 mmHg) to react for 12 hours the mixture was extracted three times with ethyl acetate dried over anhydrous magnesium sulfate After removal of the drying agent the solvent was removed under reduced pressure The obtained residue was mixed with 450 ml of 5% sodium hydroxide solution vigorously stirred under ice-water cooling extracted three times with ethyl acetate dried over anhydrous magnesium sulfate After removal of the drying agent the solvent was removed under reduced pressure The obtained residue was distilled under reduced pressure

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

Procedure: A mixture of 179 g of the 4,4,4-trifluorobutyrylmalonic acid ditheyl ester thus obtained, 260 ml of water and 322 mg of p-toluenesulfonic acid was refluxed with vigorous stirring for 6 hours. The reaction solution was then poured into saturated aqueous sodium hydrogencarbonate solution and extracted three times with diethyl ether. The ether layers were combined and the combined layer was washed with brine, dried over anhydrous magnesium sulfate. After the drying agent was removed, the solvent was removed under reduced pressure. The obtained residue was distilled inder reduced pressure to yield 98.8 g of the desired ethyl 4,4,4-trifluorobutyrylacetate in a yield of 74%. (b.p. 93°-97° C., 15 mmHg) thus obtained extracted three times with diethyl ether the combined layer was washed with brine dried over anhydrous magnesium sulfate After the drying agent was removed the solvent was removed under reduced pressure The obtained residue was distilled inder reduced pressure

Conditions: temp:37.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 98.8 g of the ethyl 4,4,4-trifluorobutyrylacetate thus obtained was added to 250 ml of a 10% sodium hydroxide solution and vigorously stirred for 12 hours. The pH value of the reaction solution was brought 7.5 with a 10% aqueous sulfuric acid solution. Then 250 ml of toluene, 2.86 g of sodium hydrogencarbonate and 6.43 g of hydrosulfite were added to the solution under an atmosphere of nitrogen and warmed to 37° C. 90 g of methyl glyoxal was added over 1 hour and allowed to react for 12 hours. After 50 g of sodium chloride was added to the solution, the mixture was extracted three times with ethyl acetate. The ethyl acetate layers were combined and dried over anhydrous magnesium sulfate. After removal of the drying agent, the solvent was removed under reduced pressure. The obtained residue was mixed with 450 ml of 5% sodium hydroxide solution and vigorously stirred under ice-water cooling. The pH of the solution was adjusted to 7.3 with a 10% hydrochloric acid solution and then extracted three times with ethyl acetate. The ethyl acetate layer was combined and dried over anhydrous magnesium sulfate. After removal of the drying agent, the solvent was removed under reduced pressure. The obtained residue was distilled under reduced pressure to afford 45 g of the desired (RS)-2-methyl-3-(2,2,2-trifluoroethyl)-4-oxocyclopent-2-en-1-ol in a yield 50%. to react for 12 hours the mixture was extracted three times with ethyl acetate dried over anhydrous magnesium sulfate After removal of the drying agent the solvent was removed under reduced pressure The obtained residue was mixed with 450 ml of 5% sodium hydroxide solution vigorously stirred under ice-water cooling extracted three times with ethyl acetate dried over anhydrous magnesium sulfate After removal of the drying agent the solvent was removed under reduced pressure The obtained residue was distilled under reduced pressure

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

Procedure: A mixture of 179 g of the 4,4,4-trifluorobutyrylmalonic acid ditheyl ester thus obtained, 260 ml of water and 322 mg of p-toluenesulfonic acid was refluxed with vigorous stirring for 6 hours. The reaction solution was then poured into saturated aqueous sodium hydrogencarbonate solution and extracted three times with diethyl ether. The ether layers were combined and the combined layer was washed with brine, dried over anhydrous magnesium sulfate. After the drying agent was removed, the solvent was removed under reduced pressure. The obtained residue was distilled inder reduced pressure to yield 98.8 g of the desired ethyl 4,4,4-trifluorobutyrylacetate in a yield of 74%. thus obtained extracted three times with diethyl ether the combined layer was washed with brine dried over anhydrous magnesium sulfate After the drying agent was removed the solvent was removed under reduced pressure The obtained residue was distilled inder reduced pressure

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

Procedure: To a stirred solution of Meldrum's Acid (3.0 g, 20.8 mmol) in 100 mL of CH2Cl2, 4-trifluoromethyl butyric acid (2.96 g, 20.8 mmol) was added followed by DMAP (5.08 g, 41.6 mmol) and finally DCC (4.30 g, 20.8 mmol). The reaction stirred overnight at room temperature. The mixture was then filtered and the filtrate washed with 1M HCl, H2O and Brine. The organics were then dried over sodium sulfate, filtered and concentrated to a yellow oil. The material was then dissolved in 100 mL of EtOH and refluxed overnight. The reaction mixture was concentrated and purified by column chromatography (ethyl acetate/hexanes (1:4)) to yield 1.88 g (43%) of a clear oil.: 1H NMR (CDCl3, 400 MHz) δ 4.24–4.10 (q, 2H, J=7.14), 3.45 (s, 2H), 2.93–2.73 (t, 2H, J=7.88), 2.52–2.28 (m, 2H), 1.31–1.20 (t, 3H, J=7.14) The mixture was then filtered the filtrate washed with 1M HCl, H2O and Brine The organics were then dried over sodium sulfate filtered concentrated to a yellow oil The material was then dissolved in 100 mL of EtOH refluxed overnight The reaction mixture was concentrated purified by column chromatography (ethyl acetate/hexanes (1:4))