Triethylamine → HCID 86758983, compound

To an oven-dried flask was added potassium ethyl malonate (3.66 g, 21.5 mmol) and freshly distilled acetonitrile (70 mL). The mixture was cooled to 10° C. to 15° C. and stirred under an atmosphere of nitrogen and to it added anhydrous magnesium chloride (2.44 g, 25.7 mmol) and triethylamine (2.05 g, 20.3 mmol). The mixture was then stirred at room temperature under nitrogen for 2.5 hours. The resultant white slurry was recooled to 0° C. and 2,4,5-trifluorobenzoyl chloride was added over a period of 15 minutes, followed by more triethylamine (0.23 g, 2.3 mmol). The mixture was then stirred at room temperature overnight under nitrogen. Acetonitrile was then removed in vacuo and toluene (30 mL) was added. The mixture was reconcentrated and more toluene (60 mL) then added. Hydrochloric acid (1.5 M, 40 mL) was cautiously added, ensuring that the temperature did not exceed 25° C., and the aqueous layer separated. The organic fraction was washed with 1.5 M HCl (2×25 mL) and water (2×25 mL), dried over MgSO4, and solvent removed in vacuo to afford 3-oxo-3-(2,4,5-trifluoro-phenyl-propionic acid ethyl ester as a pale orange solid (2.35 g, 9.55 mmol, 94%). Rf 0.55 (CH2C2), mp 57-59° C. FTIR, νmax/cm −1 3088, 2990, 1735, 1687, 1514, 1429, 1321, 1205, 1140, 1055, 897, 807. 1 H NMR (CDCl3, 250 MHz), δ/ppm [12.69 (s), 5.81 (s) and 3.92 (d, J=3.9 Hz)] (2 H, keto-enol tautomers); 7.74 (1 H, m, Ar H); 6.98 (1 H, m, Ar H); 4.24 and 4.17 (2 H, both q, 3J=7.1 Hz); 1.31 and 1.24 (3 H, both t, 3J=7.1 Hz). 13C{1 H}NMR (CDCl3, 63 MHz), δ/ppm 187.8 (C=O); 173.0 (—HC=C); 166.9 (CO2Et); 163.7, 159.8, 155.9, 151.8, 149.0, 145.3, 120.9 (quat. Ar C); 118.7, 106.6 (Ar C—H); 92.9 (HC=C); 61.4 and 60.6 (—OCH2); 49.4 (—OCCH2CO—); 14.0 (—CH3). 19FNMR (CDCl3, 235 MHz) δ/ppm −110.6 and −111.7 (m, Ar F); −123.5 and −129.0 (m, Ar F); −140.5 and −141.7 (m, Ar F). λmax/nm (δ/dm3mol−1cm−1) 295 (4781), 281 (3962), 240 (5191). HRMS (EI), M+/z C11H9F3O3 (M−) requires 246.0504; found 246.0514.

1. temperatureThe mixture was cooled to 10° C. to 15° C.
2. stirringThe mixture was then stirred at room temperature under nitrogen for 2.5 hours
3. customwas recooled to 0° C.
4. stirringThe mixture was then stirred at room temperature overnight under nitrogen
5. customAcetonitrile was then removed in vacuo and toluene (30 mL)
6. additionwas added
7. additionmore toluene (60 mL) then added
8. additionHydrochloric acid (1.5 M, 40 mL) was cautiously added
9. customdid not exceed 25° C.
10. customthe aqueous layer separated
11. washThe organic fraction was washed with 1.5 M HCl (2×25 mL) and water (2×25 mL)
12. dry with materialdried over MgSO4, and solvent
13. customremoved in vacuo

ORD record

ord-b791fa9f0a104f8db9993dc257a5b7fc

Source dataset

uspto-grants-2003_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06566520B2