Reaction #9358

Reaction equation

t-butyl nitrite

amine

8-amino-3,4-dihydro-2H-naphthalen-1-one

BF3.OEt2

→

8-fluoro-3,4-dihydro-2H-naphthalen-1-one

Solvents

CH2Cl2

pentane

CH2Cl2

CH2Cl2

Conditions

Workup

1. 1
   Filtrationfiltered
2. 2
   Otherthe solids were collected
3. 3
   Washwashed with ether
4. 4
   Otherdried under vacuum
5. 5
   OtherThe solids were placed in a flask
6. 6
   Temperatureheated to 115° C. for 10–15 min.
7. 7
   workup.ADDITIONfollowed by addition of 2N NaOH and CHCl3
8. 8
   FiltrationThe suspension was filtered
9. 9
   Extractionthe aqueous phase was extracted with CHCl3
10. 10
    Dryingdried over MgSO4
11. 11
    Filtrationfiltered
12. 12
    Otherpurified by chromatography on SiO2 with 15% EtOAc

Procedure

The amine (Intermediate J3, 1.83 g, 11.3 mmol) in CH2Cl2 (17 mL) was added to BF3.OEt2 (2.80 mL, 22.1 mmol) at −15° C. More CH2Cl2 (20 mL) was added to the precipitate. Next, t-butyl nitrite (1.8 mL, 12.9 mmol) in CH2Cl2 (20 mL) was added at −15° C. and stirred for 10 min. and at 0° C. for 20 m. The mixture was diluted with pentane (40 mL), filtered and the solids were collected, washed with ether, and dried under vacuum. The solids were placed in a flask and heated to 115° C. for 10–15 min. followed by addition of 2N NaOH and CHCl3. The suspension was filtered and the aqueous phase was extracted with CHCl3. The organic layers were combined, dried over MgSO4, filtered and purified by chromatography on SiO2 with 15% EtOAc:Hx. The product, 8-fluoro-3,4-dihydro-2H-naphthalen-1-one (Intermediate J4) was isolated; 750 mg (40%).

Source