N,N-Dimethylaniline → Methyl 8-chloro-6-oxo-2,3,4,6-tetrahydro-1H-quinolizine-9-carboxylate

HRID 910152Notes

Reaction equation

HRID 910152 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]=1

Participants

4

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 54705865Methyl 8-hydroxy-6-oxo-2,3,4,6-tetrahydro-1H-quinolizine-9-carboxylate

Product 1

HCID 817846Methyl 8-chloro-6-oxo-2,3,4,6-tetrahydro-1H-quinolizine-9-carboxylate

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

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. customquenched with ice
  3. concentrationThe aqueous solution was concentrated in vacuo
  4. customthe residue triturated in 20% MeOH/DCM
  5. customInorganic salts were removed by filtration
  6. customthe filtrate evaporated to dryness
  7. customThe resulting solid was purified by flash chromatography

Sources & evidence

ORD record
ord-5e667cfbd98b4372b6ef95f8a640d267
Source dataset
uspto-grants-2011_09
Patent number
US08022057B2

Reaction notes

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