Thionyl Chloride → 3-(1-Acetyl-4-piperidinyl)propionyl chloride

Participants

Reaction Steps

Into thionyl chloride (300 ml) was added 3-(1-acetyl-4-piperidinyl)propionic acid (88.2 g, 0.443 mol) in small portions under ice cooling. After the resulting mixture was stirred at room temperature for 10 minutes, the thionyl chloride was evaporated under reduced pressure at 25° C. The resulting residue was mixed with diethyl ether and was evaporated under reduced pressure to leave a yellow solid residue. An additional diethyl ether was added to the residue and the solid substance was subjected to pulverization by the use of a spatula, followed by evaporation under reduced pressure to obtain a crude product of 3-(1-acetyl-4-piperidinyl)propionyl chloride as a yellow powder. To a suspension of this yellow powder and 1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinoline-4-one (64.0 g, 0.369 mol) in 1,2-dichloroethane (200 ml) was added aluminum chloride (162 g, 1.21 mol) in small portions at room temperature. After stirring at room temperature for 12 hours, the reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried with anhydrous magnesium sulfate, and then evaporated under reduced pressure to remove the solvents, thereby obtaining an oily pale yellow substance. This oily substance was purified by column chromatography on silica gel (eluent: ethyl acetate-methanol=9:1) and crystallization from ethanol and diethyl ether to obtain 123 g of 8-[3-(1-acetyl-4-piperidinyl)-1-oxopropyl]-1,2,5,6-tetrahydro-4H-pyrrolo-[3,2,1-ij]quinolin-4-one, as colorless crystals having the melting point of 157-159° C.

Provenance & Evidence