Ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoate

Ethyl 4, 4, 4-trifluoro-3-oxobutanoate (30 g, 162.9 mmol) was added to a solution of triethoxymethane (72.4 g, 488.8 mmol) in acetic anhydride (50 mL). Ethyl trifluoroacetoacetate (0.036 mol), triethyl orthoformate (0.059 mol) andAcetic anhydride (0.108πο1) was added to a three-necked flask and refluxed for 6 hours, After completion of the reaction, the mixture was distilled under reduced pressure and the mixture was collected at 98 to 105 ° C to obtain 7.4 g of a pale yellow oily liquid, Yield 92.6percent.[00520] To a solution of ethyl-(4, 4, 4, -trifluoro)-3-oxobutyrate (20 g, 0.11 mol) in acetic anhydride (33.3 g, 0.33 mol) was added triethyl orthoformate (24.1 g, 0.165 mol). The reaction mixture was heated at 120 In a 500 mL four-necked flask, trifluoroacetoacetate ethyl-(4, 4, 4-trifluoro)-3-oxobutyrate (18400 mg, 100 mmol), triethylorthoformate (44400 mg, 300 mmol) and acetic anhydride(61200 mg, 600 mmol) were added and heated at 120 C for 6 h. Then, the solvent was removed and the product was then distilledunder vacuum over a column to give a colorless liquid, yield 90percent.78.3 g (0.425 mol) of ethyl trifluoroacetoacetate, 103 g (0.638 mol) of triethyl orthoformate and 130 g (1.275 mol) of acetic anhydride were placed in a 500 ml three-necked flask, Heated to 120 reaction 6h.To distillation unit will be 100 low boiling point substances removed by distillation.Then the pump vacuum to remove low boilers, The oil pump was distilled under reduced pressure to give ethyl 2-ethoxymethylene-4, 4, 4-trifluoroacetoacetate as a colorless liquid, About 81g, Yield 80percent.Stage 2Ethyl 2-[1-ethoxymethylidene]-4, 4, 4-trifluoro-3-oxobutyrate An amount of 101 g (548.5 mmol) of ethyl 4, 4, 4-trifluoro-3-oxobutyrate, 164 g (1106 mmol) of triethyl orthoformate and 114.1 g (1118 mmol) of acetic anhydride were stirred in a distillation apparatus at 120° C. for 1 hour, and then the temperature was increased to 140° C. over the course of 30 minutes. Partial cooling was followed by distillation under a membrane pump vacuum.Yield: 103.6 g (75percent of theory) 1H-NMR (CD3CN) 1.2-1.4 (m, 6H), 4.2-4.4 (m, 4H), 7.75-7.95 (1H)A mixture of ethyl-4, 4, 4-trifluoroacetoacetate (19, 37.8 g, 206 mmol), triethyl orthoformiate (45.6 g, 308 mmol) and acetic anhydride (58.1 mL, 615 mmol) was heated at 120 °C for 2 h and then at 140 °C for 5 h. Low boiling solvents were removed in vacuo. The residue was distilled under vacuum (ca. 10 mm Hg). After removing low boiling fraction (bp 70 - 90 °C at 10 mm Hg) the main fraction (bp 110 - 115 °C at ca. 10 mm Hg) was collected as a light yellow, thick oil. Yield: 31.57 g (64percent) as an E/Z mixture. The acetic anhydride (367.6 g, 3.6 moles) is heated to 100-105° C., to which a mixture of crude ethyl trifluoroacetoacetate (˜0.96 mole) and triethyl orthoformate (266.8 g, 1.8 moles) is added drop-wise. A solution of ethyl trifluoroacetoacetate (0.036 mol)Triethyl orthoformate (0.059 mol) and acetic anhydride (0.108 mol) were added to a 100 ml three-necked flask, Reflux reaction for 6 hours, After the completion of the reaction with a vacuum pump distillation, A fraction of 98 to 105 ° C was collected, To give 7.4 g of a pale yellow oily liquid in a yield of 92.6percent.A mixture of 18.4 g (0.1 mol) of ethyl trifluoroacetoacetate, 60 g (0.4 mol) of ethyl orthoformate was refluxed at 120 °C for 24 hours, providing the removal of volatile products from reaction mixture. The liquid remaining in the flask was distilled in vacuum. The first fraction (13.5 g, 56 percent yield) contained ethyl ethoxymethylenetrifluoroacetoacetate as a colorless liquid collected at 130-132 °C/10 Torr. The second fraction (10 g, 30 percent) as yellow liquid of compound 3 was collected at 157-159 °C/10 Torr. NMR data of compound 3: 1H NMR (500 MHz, CDCl3): δ 1.25 (t, 3H, CH3, 3JHH = 7 Hz), 1.34 (t, 6H, 2CH3, 3JHH = 7 Hz), 3.84 and 3.93 (both m, 2H, CH2O), 4.30-4.35 (m, 4H, 2CH2), 6.17 (s, 1H, CHO), 7.61 (s, 1H, CH). 19F NMR (376 MHz, CDCl3/C6F6): δ 95.1 (s, CF3). 13C NMR (125 MHz, CDCl3): δ 13.75, 14.12, 14.88, 61.28, 61.98, 65.56, 96.13, 110.48, 119.16 (q, 1JCF = 275 Hz), 119.46, 130.59, 147.55 (q, 2JCF = 38 Hz), 163.34, 163.40. HRMS calcd for C14H18F3O6 [M+H]+ 339.1050; found 339.1050.

Molecular Weight:240.18
XLogP3:2.1
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:6
Exact Mass:240.06094331
Monoisotopic Mass:240.06094331
Topological Polar Surface Area:52.6
Heavy Atom Count:16
Complexity:294
Defined Bond Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes