Reaction #433638

Reaction equation

8-(3-fluoro-benzyloxy)-1,3-dihydro-benzo[d]azepin-2-one

sodium acetate

→

3-acetyl-8-(3-fluoro-benzyloxy)-1,3-dihydro-benzo[d]azepin-2-one

Yield 77.7%

Solvents

acetic acid anhydride

Conditions

Workup

1. 1
   Temperaturethe reaction mixture was cooled
2. 2
   Otherevaporated under reduced pressure
3. 3
   workup.ADDITIONThe residue was treated with 1.5 ml of ice/water and 4 ml of ethyl acetate
4. 4
   OtherThe aqueous layer was separated
5. 5
   Extractionre-extracted with 4 ml of ethyl acetate
6. 6
   DryingThe combined organic layers were dried over sodium sulfate
7. 7
   Otherthe solvent evaporated under reduced pressure
8. 8
   OtherFor purification
9. 9
   Otherthe crude material obtained
10. 10
    Otherwas chromatographed on silica gel using a gradient of heptane to a 4

Procedure

In a dried flask under an inert atmosphere, 103 mg (0.36 mmol) of 8-(3-fluoro-benzyloxy)-1,3-dihydro-benzo[d]azepin-2-one and 72 mg (0.9 mmol) of sodium acetate were suspended in 0.3 ml of acetic acid anhydride. The solution was heated to 140° C. for 4 h. For the working-up, the reaction mixture was cooled, then evaporated under reduced pressure. The residue was treated with 1.5 ml of ice/water and 4 ml of ethyl acetate. The aqueous layer was separated and re-extracted with 4 ml of ethyl acetate. The combined organic layers were dried over sodium sulfate, thereafter the solvent evaporated under reduced pressure. For purification, the crude material obtained was chromatographed on silica gel using a gradient of heptane to a 4:1-mixture of heptane and ethyl acetate as the eluent. There were obtained 91 mg (77% of theory) of 3-acetyl-8-(3-fluoro-benzyloxy)-1,3-dihydro-benzo[d]azepin-2-one as a light yellow solid; MS: m/e=325 (M)+.

Source