Reaction #8587

Reaction equation

Boron trifluoride

7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridine

acetic anhydride

→

1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]ethanone

Yield 77.0%

Solvents

toluene

Conditions

Workup

1. 1
   Temperatureto reflux for 3.5 hours
2. 2
   Otherquenched by the dropwise addition of aqueous sodium bicarbonate
3. 3
   workup.ADDITIONEther was added
4. 4
   Washthe organic layer was washed with brine
5. 5
   ExtractionThe aqueous layer was extracted with ether
6. 6
   Dryingthe-combined organics were dried over magnesium sulfate
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated
9. 9
   OtherThe residue was purified by recrystallization from ethyl acetate-hexanes

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, 1 H), 7.59 (m, 2 H). 7.45 (dd,1 H), 7.26–7.13 (m 3 H), 2.15 (s, 3 H); 19F NMR (CDCl3) δ −112.06; MS m/z 289 (M+1).

Source