Sodium Acetate → 3-Acetyl-2-indolizinecarboxylic acid, methyl ester

HRID 704073Notes

Reaction equation

HRID 704073 reaction equation
[CH:1]1[C:2]([C:10]([O:12][CH3:13])=[O:11])=[CH:3][N:4]2[C:9]=1[CH:8]=[CH:7][CH:6]=[CH:5]2.[C:14]([O-])(=[O:16])[CH3:15].[Na+]>C(OC(=O)C)(=O)C>[C:14]([C:3]1[N:4]2[C:9]([CH:8]=[CH:7][CH:6]=[CH:5]2)=[CH:1][C:2]=1[C:10]([O:12][CH3:13])=[O:11])(=[O:16])[CH3:15]

Participants

4

Reactant 2

HCID 517045Sodium AcetateHCID 600232Methyl indolizine-2-carboxylate

Product 1

HCID 157133103-Acetyl-2-indolizinecarboxylic acid, methyl esterYield 99.2%

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent2×

Procedure

A stirred solution of 2-indolizinecarboxylic acid, methyl ester (91.42 g, 0.522 mole) and anhydrous sodium acetate (42.53 g, 0.52 mole) in acetic anhydride (1.1 L) was refluxed, under anhydrous conditions, for 48 hours. After cooling most of the acetic anhydride was evaporated in vacuo. The resulting residue (150 ml) was cooled in an ice water bath and methanol (140 ml) was added to destroy the remaining acetic anhydride. The resulting mixture was poured into water (1.1 L) and the product was extracted with diethyl ether, three times. The ethereal layer was washed with saturated sodium bicarbonate solution, three times, with water, two times, and was dried over magnesium sulfate. Evaporation of solvent yielded 112 g of crude 3-acetyl-2-indolizinecarboxylic acid, methyl ester which was chromatographed on silica gel (3 kg) using 10% acetone in benzene as eluant, to afford the pure compound (85.5 g). For analysis, the product was recrystallized from a mixture of diethyl ether and petroleum ether.

Workup

  1. customwas evaporated in vacuo
  2. temperatureThe resulting residue (150 ml) was cooled in an ice water bath
  3. additionmethanol (140 ml) was added
  4. customto destroy the remaining acetic anhydride
  5. additionThe resulting mixture was poured into water (1.1 L)
  6. extractionthe product was extracted with diethyl ether, three times
  7. washThe ethereal layer was washed with saturated sodium bicarbonate solution, three times, with water, two times
  8. dry with materialwas dried over magnesium sulfate
  9. customEvaporation of solvent

Sources & evidence

ORD record
ord-0beb2aa862cc46a58b5647858ef43758
Source dataset
uspto-grants-1991_01
Patent number
US04985560

Reaction notes

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