反应详情

温度

0 °C

To a solution of 3,4-difluorophenyl propionic acid (30.45 g; 163.6 mmol) and 2 drops of DMF in CH2Cl2 (200 mL) was added oxalyl chloride (41.4 g, 327 mmol) over 20 min. The resulting solution was stirred for 24 hr and concentrated in vacuo (chased 1×PhMe, ca. 100 mL). The residue was dissolved in CS2 (300 mL), cooled to 0° C. and AlCl3 (76.4 g, 573 mmol) was added over 10 min. The mixture was stirred 30 min at 0° C., then heated under reflux for 4 hr. Upon cooling to room temperature the solution was carefully poured onto crushed ice, the carbon disulfide layer was separated and the aqueous layer extracted with EtOAc. Combined organics were dried over MgSO4 and the concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.50 (t, 1H, J=8.0 Hz), 7.24 (t, 1H, J=6.6 Hz), 3.09 (t, 2H, J=5.5 Hz), 2.72-2.69 (m, 2H).

1. concentrationconcentrated in vacuo (chased 1×PhMe, ca. 100 mL)
2. dissolutionThe residue was dissolved in CS2 (300 mL)
3. stirringThe mixture was stirred 30 min at 0° C.
4. temperatureheated
5. temperatureunder reflux for 4 hr
6. temperatureUpon cooling to room temperature the solution
7. additionwas carefully poured
8. customonto crushed ice
9. customthe carbon disulfide layer was separated
10. extractionthe aqueous layer extracted with EtOAc
11. dry with materialCombined organics were dried over MgSO4
12. concentrationthe concentrated in vacuo
13. customThe residue was purified by flash chromatography (EtOAc/hexanes)