Boron trifluoride → 1-(7-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl)ethanone

HRID 1373785

Reaction equation

HRID 1373785 reaction equation
[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[CH:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.[C:18](OC(=O)C)(=[O:20])[CH3:19].B(F)(F)F>C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:10]([C:18](=[O:20])[CH3:19])=[C:6]2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6356Boron trifluorideHCID 7918Acetic AnhydrideHCID 111841947-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine

Product 1

HCID 223500461-(7-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl)ethanoneYield 77%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridine (10.0 g, 40.5 mmol) in toluene (225 mL) at room temperature was added acetic anhydride (4.6 mL, 48.6 mmol). Boron trifluoride diethyletherate (5.6 mL, 44.6 mmol) was then added dropwise and the resultant solution was heated to reflux for 3.5 hours. The reaction mixture was cooled to room temperature and quenched by the dropwise addition of aqueous sodium bicarbonate. Ether was added and the organic layer was washed with brine. The aqueous layer was extracted with ether and the combined organics were dried over magnesium sulfate, filtered and concentrated. The residue was purified by recrystallization from ethyl acetate-hexanes to give 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]ethanone (9.0 g, 77%) as redish needles. 1H NMR (CDCl3): δ 8.41 (d, 1H), 7.59 (m, 2H), 7.45 (dd, 1H), 7.26–7.13 (m 3H), 2.15 (s, 3H); 19F NMR (CDCl3) δ −112.06; MS m/z 289 (M+1).

Workup

  1. temperatureto reflux for 3.5 hours
  2. customquenched by the dropwise addition of aqueous sodium bicarbonate
  3. additionEther was added
  4. washthe organic layer was washed with brine
  5. extractionThe aqueous layer was extracted with ether
  6. dry with materialthe combined organics were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by recrystallization from ethyl acetate-hexanes

Sources & evidence

ORD record
ord-8122aac7b42946339159d71d7bdc24d2
Source dataset
uspto-grants-2007_01
Patent number
US07163940B2

Linked notes

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