Reaction #47948

Reaction equation

(1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

1-bromo-3-chloropropane

→

title compound

(1S,5R)-3-(3-Chloropropyl)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Solvents

tetrahydrofuran

triethylamine

Conditions

Workup

1. 1
   Temperaturethe resulting mixture was refluxed for 16 hours
2. 2
   Concentrationwas concentrated in vacuo
3. 3
   workup.ADDITIONdiluted with ethyl acetate
4. 4
   Washwashed with a saturated solution of NaHCO3 in water and brine
5. 5
   Dryingdried over anhydrous Na2SO4
6. 6
   Concentrationconcentrated under reduced pressure
7. 7
   OtherThe crude product was purified by chromatography (silica gel)
8. 8
   Washeluting with cyclohexane/EtOAc 8:2

Procedure

To a solution of (1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (P13, 426 mg) in dry tetrahydrofuran (9 mL), triethylamine (0.79 mL) and 1-bromo-3-chloropropane (0.37 mL) were added and the resulting mixture was refluxed for 16 hours. After cooling at room temperature it was concentrated in vacuo, diluted with ethyl acetate, washed with a saturated solution of NaHCO3 in water and brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by chromatography (silica gel) eluting with cyclohexane/EtOAc 8:2 to give the title compound as yellow oil (582 mg).

Source