N,N-Dimethylaniline → Methyl 7-chloro-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylate

HRID 910144Notes

Reaction equation

HRID 910144 reaction equation
O[C:2]1[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]2[N:5]([CH2:6][CH2:7][CH2:8]2)[C:4](=[O:15])[CH:3]=1.P(Cl)(Cl)([Cl:18])=O.CN(C)C1C=CC=CC=1>>[Cl:18][C:2]1[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]2[N:5]([CH2:6][CH2:7][CH2:8]2)[C:4](=[O:15])[CH:3]=1

Participants

4

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 54694252Methyl 7-hydroxy-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylate

Product 1

HCID 57689810Methyl 7-chloro-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylateYield 69%

Procedure

Compound 1a (8.0 g, 38.3 mmol) was stirred in phosphorous oxychloride (20 mL, 218 mmol) at RT. Dimethylaniline (1 mL, 7.9 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 6.02 g (69%) of compound 1b as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 6.46 (s, 1H), 3.99 (t, 2H, J=7.6 Hz), 3.78 (s, 3H), 3.30 (t, 2H, J=7.6 Hz), 2.04-2.14 (m, 2H). MS (ES) [m⇄H] calc'd for C10H10ClNO3, 228, 230. found 228, 230.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. customquenched with ice
  3. concentrationThe aqueous solution was concentrated in vacuo
  4. customwere removed by filtration
  5. concentrationOrganics were concentrated
  6. custompurified by silica gel chromatography (75% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-c5bfcb715e5b4dd6b509c355cf77a22d
Source dataset
uspto-grants-2011_09
Patent number
US08022057B2

Reaction notes

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