Reaction #41036

Reaction equation

4-(5-trifluoromethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-butyraldehyde

(1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane

AcOH

NaBH(AcO)3

dichloroethane

→

title compound

Yield 76.0%

5-(trifluoromethyl)-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2,4(1H,3H)-pyrimidinedione hydrochloride

Yield 76.0%

Solvents

Ethyl acetate

Conditions

Workup

1. 1
   Washthe solution was washed with aqueous saturated NaHCO3
2. 2
   DryingThe organic phase was dried (Na2SO4)
3. 3
   Otherevaporated
4. 4
   OtherThe crude was purified by flash chromatography with DCM-MeOH—NH4OH (95-5-1)

Procedure

To a solution of 4-(5-trifluoromethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-butyraldehyde (Prep24, 22 mg, 0.09 mmol) in dichloroethane (1 mL), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 204 mg, 0.09 mmol), AcOH (7.9 mg, 0.13 mmol) and NaBH(AcO)3 (22 mg, 0.18) were added and the mixture was stirred at room temperature overnight. Ethyl acetate was added and the solution was washed with aqueous saturated NaHCO3. The organic phase was dried (Na2SO4) and evaporated. The crude was purified by flash chromatography with DCM-MeOH—NH4OH (95-5-1) to give the title compound (31 mg, 76% yield) as a free base.

Source