N,N-Dimethylaniline → Ethyl 7-chloro-6-methyl-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylate

Reaction equation

O[C:2]1[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:9]2[N:5]([CH2:6][CH2:7][CH2:8]2)[C:4](=[O:16])[C:3]=1[CH3:17].P(Cl)(Cl)([Cl:20])=O.CN(C)C1C=CC=CC=1>>[Cl:20][C:2]1[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:9]2[N:5]([CH2:6][CH2:7][CH2:8]2)[C:4](=[O:16])[C:3]=1[CH3:17]

Participants

Reactant 3

HCID 949N,N-Dimethylaniline

HCID 24813Phosphorus oxychloride

HCID 54691177Ethyl 7-hydroxy-6-methyl-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylate

Product 1

HCID 57689808Ethyl 7-chloro-6-methyl-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylateYield 63%

Procedure

Compound 8b (659 mg, 2.8 mmol) was stirred in phosphorous oxychloride (1.5 mL, 15.8 mmol) at RT. Dimethylaniline (0.07 mL, 0.56 mmol) was added and the reaction stirred 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. The residue was taken up in a 20% MeOH/CH2Cl2 and insoluble inorganic salts were removed by filtration. Organics were concentrated and purified by silica gel chromatography (75% EtOAc/CH2Cl2) to give 450 mg (63%) of compound 8c as a white solid. MS (ES) [m+H] calc'd for C12H14ClNO3, 256. found 256.