反应详情

To a solution of ethyl 2-chloro-4-(4-chlorophenyl)-3-oxobutanoate (70.8 g, 257 mmol) in IPA (2.96 L) was added thioisonicotinamide (71.1 g, 515 mmol) and the resulting mixture was refluxed for 3 days. The reaction was cooled and concentrated in vacuo and the residue was partitioned between DCM (300 ml) and saturated sodium bicarbonate solution (200 mL). The layers were separated and the aqueous layer was extracted with DCM (100 mL). The combined DCM layers were washed with brine (100 mL), dried over MgSO4, filtered, and concentrated in vacuo to give crude product which was purified by silica gel chromatography (ethyl acetate/DCM=0/100→40/60) followed by recrystallization from ethyl acetate/hexanes to give 33 g of the title compound as yellow crystals. (36% yield). LC/MS (FA) ES+ 359. 1H NMR (400 MHz, CDCl3) δ: 8.74-8.72 (m, 2H), 7.81-7.80 (m, 2H), 7.36-7.32 (m, 2H), 7.27-7.23 (m, 2H), 4.54 (s, 2H), 4.38 (q, 2H, J=7.2 Hz), 1.40 (t, 3H, J=7.2 Hz).

1. temperaturethe resulting mixture was refluxed for 3 days
2. temperatureThe reaction was cooled
3. concentrationconcentrated in vacuo
4. customthe residue was partitioned between DCM (300 ml) and saturated sodium bicarbonate solution (200 mL)
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with DCM (100 mL)
7. washThe combined DCM layers were washed with brine (100 mL)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give crude product which
12. customwas purified by silica gel chromatography (ethyl acetate/DCM=0/100→40/60)
13. customfollowed by recrystallization from ethyl acetate/hexanes