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

HRID 910157Notes

Reaction equation

HRID 910157 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

4

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 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.

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-2f904665b28146c998d3c112c02aee76
Source dataset
uspto-grants-2011_09
Patent number
US08022057B2

Reaction notes

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