Acetic Anhydride → 1-[2-(Propan-2-yl)pyrazolo[1,5-a]pyridin-3-yl]ethan-1-one

HRID 731745Notes

Reaction equation

HRID 731745 reaction equation
[CH:1]([C:4]1[CH:12]=[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][N:6]2[N:5]=1)([CH3:3])[CH3:2].[C:13](OC(=O)C)(=[O:15])[CH3:14]>S(=O)(=O)(O)O>[CH:1]([C:4]1[C:12]([C:13](=[O:15])[CH3:14])=[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][N:6]2[N:5]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 113786582-Isopropylpyrazolo[1,5-a]pyridine

Product 1

HCID 159338551-[2-(Propan-2-yl)pyrazolo[1,5-a]pyridin-3-yl]ethan-1-oneYield 87%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidCatalyst

Procedure

2-Isopropyl-pyrazolo[1,5-a]pyridine (10.00 g, 66.7 mmol), acetic anhydride (100 ml), and concentrated sulfuric acid (10 drops) were combined and stirred for 3 hours at reflux. The reaction mixture was cooled to room temperature and poured into ice water (300 ml). The mixture was quenched with 2 N sodium hydroxide until the pH>10, and the quenched solution was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified by silica gel flash chromatography (0 to 40% ethyl acetate in hexanes) to give 11.8 g (87%) of 1-(2-isopropyl-pyrazolo[1,5-a]pyridin-3-yl)-ethanone. 1H-NMR (250 MHz, DMSO-d6) δ 8.47 (d, J=6.8 Hz, 1H), 8.12 (d, J=9.0 Hz, 1H), 7.38 (t, J=7.3 Hz, 1H), 6.89 (t, J=6.0 Hz, 1H), 3.76 (sept, J=6.9 Hz, 1H), 2.60 (s, 3H), 1.39 (d, J=6.8 Hz, 6H); LC/MS 203.3 m/z (M+H+).

Workup

  1. temperatureat reflux
  2. customThe mixture was quenched with 2 N sodium hydroxide until the pH>10
  3. extractionthe quenched solution was extracted with ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by silica gel flash chromatography (0 to 40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-0a4f04d9acb64f4fb3bc8f74ff2c6840
Source dataset
uspto-grants-2009_09
Patent number
US07585875B2

Reaction notes

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