Acetic Anhydride → Methyl indolizine-2-carboxylate

HRID 519388Notes

Reaction equation

HRID 519388 reaction equation
C(OC(=O)C)(=O)C.O[CH:9]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1)[C:10](=[CH2:15])[C:11]([O:13][CH3:14])=[O:12]>C(=O)(O)[O-].[Na+]>[CH:9]1[C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:15][N:17]2[C:16]=1[CH:21]=[CH:20][CH:19]=[CH:18]2

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 11008779Methyl beta-hydroxy-alpha-methylene-2-pyridinepropanoate

Product 1

HCID 600232Methyl indolizine-2-carboxylateYield 35%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent2×

Procedure

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with acetic anhydride (80 mL) and 127a (6.68 g, 34.6 mmol). The reaction mixture was heated at reflux under nitrogen for 4 h. After this time the reaction was cooled to room temperature, poured onto the mixture of ice (100 g) and saturated aqueous sodium bicarbonate solution (200 mL), and stirred for 1 h. The resulting solution was neutralized with saturated aqueous sodium bicarbonate and extracted with methylene chloride (3×200 mL). The combined organic extract was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 10:1 petroleum ether/ethyl acetate (10:1) to afford 127b as a white solid (2.1 g, 35%). MS-ESI: (M+H)+ 176.2. 1H NMR (500 MHz, CDCl3) δ 7.86-7.84 (m, 1H), 7.79 (d, J=1.0 Hz, 1H), 7.36-7.34 (m, 1H), 6.82 (s, 1H), 6.70-6.66 (m, 1H), 6.55-6.51 (m, 1H), 3.88 (s, 3H).

Workup

  1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux under nitrogen for 4 h
  4. extractionextracted with methylene chloride (3×200 mL)
  5. extractionThe combined organic extract
  6. dry with materialwas dried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica-gel column chromatography
  9. washeluting with 10:1 petroleum ether/ethyl acetate (10:1)

Sources & evidence

ORD record
ord-4a1f5c6cd465429388b12480dbb74f59
Source dataset
uspto-grants-2015_08
Patent number
US09115152B2

Reaction notes

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