Hydrochloric Acid → 6-chloro-1-(2,4-dichlorobenzoyl)-2,3-dihydro-3-methyl-4(1H)-quinolinone

Temperature

0 °C

To a cooled (-20° C. to -15° C.) solution of diisopropylamine (4.7 g) in anhydrous tetrahydrofuran (100 ml) was added dropwise n-hexane solution (29 ml) of 1.6 N butyl lithium over a 30-minute period in a nitrogen atmosphere, and stirring was continued for 30 minutes after the mixed solution was returned to 0° C. Then the solution was cooled to -75° C. with acetone-dry ice and 15 g of 6-chloro-1-(2,4-dichlorobenzoyl)-2,3-dihydro-4(1H)-quinolinone dissolved in 150 ml of anhydrous tetrahydrofuran was added dropwise over a 1-hour period. The reaction mixture was stirred for another 1 hour at -75° C., and methyl iodide (18 g) was added dropwise with stirring over a 30-minute period. The reaction mixture was then slowly warmed to 0° C. over two hour, and acidified under cooling with 2 N hydrochloric acid to be weakly acidic. The reaction mixture was poured into 300 ml of water, then shaken with ethyl acetate (500 ml). The organic layer was washed once with saturated aqueous NaCl solution (200 ml) and dried over anhydrous sodium sulfate. Ethyl acetate was removed in vacuo and the residue was subjected to silica gel column chromatography using a hexane-ethyl acetate mixture (4:1) to obtain 6-chloro-1-(2,4-dichlorobenzoyl)-2,3-dihydro-3-methyl-4(1H)-quinolinone (yield 7.8 g) as white crystal.

1. customwas returned to 0° C
2. additionwas added dropwise over a 1-hour period
3. stirringThe reaction mixture was stirred for another 1 hour at -75° C.
4. stirringwith stirring over a 30-minute period
5. washThe organic layer was washed once with saturated aqueous NaCl solution (200 ml)
6. dry with materialdried over anhydrous sodium sulfate
7. customEthyl acetate was removed in vacuo

ORD record

ord-98889cd2bf424b07852b54cd6330bcf4

Source dataset

uspto-grants-1991_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05077410