N,N-Dimethylaniline → Methyl 8-chloro-6-oxo-2,3,4,6-tetrahydro-1H-quinolizine-9-carboxylate
Reaction equation
O[C:2]1[C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]2[N:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[C:4](=[O:16])[CH:3]=1.P(Cl)(Cl)([Cl:19])=O.CN(C)C1C=CC=CC=1>>[Cl:19][C:2]1[C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]2[N:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[C:4](=[O:16])[CH:3]=1Participants
4
Procedure
Methyl 8-hydroxy-6-oxo-2,3,4,6-tetrahydro-1H-quinolizine-9-carboxylate (7a, 2 g, 9.52 mmol, 1 eq) was suspended in phosphorous oxychloride (5.3 ml, 57 mmol, 6 eq) and dimethylaniline (242 μl, 1.9 mmol, 0.2 eq) under nitrogen and stirred at RT for 16 h. The solution was concentrated in vacuo, quenched with ice and made basic with sat. NaHCO3 solution. The aqueous solution was concentrated in vacuo and the residue triturated in 20% MeOH/DCM. Inorganic salts were removed by filtration and the filtrate evaporated to dryness. The resulting solid was purified by flash chromatography using 75% EtOAc/DCM as eluent to give the title compound as a white solid. (1.43 g, 63%) [M+H] calc'd for C11H12ClNO3, 242. found, 242