Phosphorus oxychloride → Methyl-2-(3-fluoro-2-methyl-benzyl)-3-formyl-1-phenyl-indolizine-7-carboxylate

HRID 1963054Notes

Reaction equation

HRID 1963054 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][O:7][C:8]([C:10]1[CH:11]=[CH:12][N:13]2[C:17]([CH:18]=1)=[C:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:15]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=1[CH3:33])=[CH:14]2)=[O:9].[C:34]([O-])(=[O:36])C.[Na+]>CN(C=O)C.O>[CH3:6][O:7][C:8]([C:10]1[CH:11]=[CH:12][N:13]2[C:17]([CH:18]=1)=[C:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:15]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=1[CH3:33])=[C:14]2[CH:34]=[O:36])=[O:9]

Participants

6

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 517045Sodium AcetateHCID 67771873Methyl-2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-7-carboxylate

Product 1

HCID 88414465Methyl-2-(3-fluoro-2-methyl-benzyl)-3-formyl-1-phenyl-indolizine-7-carboxylateYield 58.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Conditions

Temperature
60 °C

Procedure

To phosphorus oxychloride (0.35 ml, 3.82 mmol) cooled at 0° C. under argon, was added dropwise anhydrous DMF (0.34 ml, 4.46 mmol) and the mixture was stirred for 5 min forming a precipitate. 1.5 ml of DMF were added and stirring was continued at 0° C. for 15 min. To this mixture was added dropwise a solution of the compound of step 2 (0.476 g, 1.27 mmol) in 5 ml of DMF, and the mixture was heated at 60° C. for 1.5 h and then stirred at room temperature overnight. A solution of sodium acetate (0.837 g) in 6.5 ml water was added, the mixture was heated at 50° C. for 1 h, and evaporated to dryness under reduced pressure. The residue was dissolved in EA, the solution was washed with a saturated solution of sodium hydrogencarbonate, water and brine, dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was purified by chromatography on silica gel (cyclohexane/EA, 100:0, then 90:10) to give 0.297 g of the title compound.

Workup

  1. customforming a precipitate
  2. stirringstirring
  3. waitwas continued at 0° C. for 15 min
  4. stirringstirred at room temperature overnight
  5. temperaturethe mixture was heated at 50° C. for 1 h
  6. customevaporated to dryness under reduced pressure
  7. dissolutionThe residue was dissolved in EA
  8. washthe solution was washed with a saturated solution of sodium hydrogencarbonate, water and brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated to dryness under reduced pressure
  12. customThe residue was purified by chromatography on silica gel (cyclohexane/EA, 100:0

Sources & evidence

ORD record
ord-b45deb4c148a46cf96b46cb7e2c29b08
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

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