| 81% |
With hydrogen fluoride; (bis-(2-methoxyethyl)amino)sulfur trufluoride In dichloromethane at 20℃; for 16h; |
|
| 75.6% |
With diethylamino-sulfur trifluoride at 60℃; for 4h; |
|
| 73% |
With potassium fluoride; formic acid; tetramethylammonium fluoride; N,N`-sulfuryldiimidazole In N,N-dimethyl-formamide at 25℃; for 4h; Inert atmosphere; |
|
| 6.04 g (75%) |
With diethylaminosulfur trifluoride |
142.A A.
A. α,α-Difluorobenzeneacetic acid, ethyl ester A mixture of ethylphenylglyoxalate (α-oxobenzeneacetic acid, ethyl ester; 7.12 g; 40 mmol) and diethylaminosulfur trifluoride (5.9 ml; 44 mmol) was stirred 18 hr at room temperature. After the reaction mixture was carefully poured onto ice and the ice melted, the resulting mixture was extracted with ether (200 ml). The organic layer was washed with saturated NaHCO3 solution (2*75 ml), brine (50 ml), dried (MgSO4) and concentrated to a yellow liquid. Distillation at 75°-80° C.; 3-4 mmHg afforded 6.04 g (75%) of the title compound of this step as a colorless liquid. 1 H NMR (CDCl3): δ 1.29 (t, J=7.5 Hz, 3H), 4.28 (q, J=7.5 Hz, 2H), 7.46 (m, 3H), 7.61 (m, 2H). 13 C NMR (CDCl3): δ 13.5, 62.8, 113.1 (t, JC-F =251 Hz), 125.1, 128.3, 130.7, 132.6 (t, JC-F2 =25.5 Hz), 163.9 (t, JC-F2 =35 Hz). |
|
With (bis-(2-methoxyethyl)amino)sulfur trufluoride at 10 - 20℃; for 20h; |
67.1
To a solution of ethyl benzoylformate (0.36 g, 2 mmol) in CH2Cl2 (10 mL) is added Deoxo- Fluor (1.1 mL, 6 mmol) at 10°C. After 20 h at 2O0C, the mixture is quenched with water (10 mL), and poured into Chem-Elut with CH2CI2 washing (10 mL). The filtrate is concentrated to give difluoro- phenyl-acetic acid ethyl ester, which is used for next step without further purification. |
| 60 %Spectr. |
Stage #1: phenylglyoxylic acid ethyl ester With tetramethylammonium fluoride Inert atmosphere; Glovebox;
Stage #2: With potassium fluoride; formic acid; N,N`-sulfuryldiimidazole In N,N-dimethyl-formamide at 20℃; Glovebox; Inert atmosphere; |
1
In a nitrogen-filled glovebox, ethyl 2-oxo-2-phenylacetate ( 17.8 mg, 0. 1 mmol) and Me4NF (37.2 mg, 0.4 mmol, 4.0 equiv) were added to Chamber B of the two-chamber reaction vessel, which was also equipped with a magnetic stir- bar. I, G-Sulfonyldiimidazole (39.6 mg, 0.2 mmol) and KF (23.2 mg, 0.4 mmol) were added to Chamber A, which was also equipped with a magnetic stir-bar. The vessel was removed from the glovebox, formic acid (0.2 mL) was added to Chamber A, and the mixture was allowed to stir at room temperature for 5 min. Anhydrous V,lV-dimethylformamide (0.5 mL) was added to Chamber B, and the reaction was allowed to stir for 24 h at room temperature. Chamber B was then diluted with dichloromethane (2.0 mL), and 4-fluoroanisole was added as an NMR standard. The reaction mixture was analyzed by 19F NMR spectroscopy; the yield of the iluorinated product was 60% compared to the internal standard. Ch b A yield: 62% |
| 60 %Spectr. |
With potassium fluoride; formic acid; tetramethylammonium fluoride; N,N`-sulfuryldiimidazole In N,N-dimethyl-formamide at 20℃; for 24h; Inert atmosphere; |
4.4.1
In a glove box filled with nitrogen, ethyl 2-oxo-2-phenylacetate (17.8 mg, 0.1 mmol) and Me4NF (37.2 mg, 0.4 mmol) , 4.0 equiv) is added to the B chamber of the double-chamber reaction vessel, which is also equipped with a magnetic stirrer.1,1'-sulfadiimidazole (39.6 mg, 0.2 mmol) and KF (23.2 mg, 0.4 mmol) are added to chamber A, which is also equipped with a magnetic stir bar.The container was removed from the set of hand work boxes, formic acid (0.2 mL) was added to chamber A, and the mixture was allowed to stir at room temperature for 5 minutes.AnhydrousN,N-dimethylformamide (0.5 mL) was added to chamber B and the reaction was allowed to stir at room temperature for 24 hours.Chamber B was then diluted with dichloromethane (2.0 mL), and 4-fluoroanisole was added as an NMR standard.The reaction mixturewas analyzedby19F NMR spectroscopy; compared to the internal standard, the yield of the fluorinated product was 60%. |
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