Reaction #50582

Reaction equation

water

N-[4,4-bis(trifluoromethyl)-2-(4-fluorophenyl)-4,5-dihydro-1H-imidazol-5-yl]-N-methylheptanamide hydrochloride

potassium carbonate

piperidine

→

title compound

Yield 22.4%

N-[4,4-bis(trifluoromethyl)-4,5-dihydro-1-methyl-2-[4-(1-piperidinyl)phenyl]-1H-imidazol-5-yl]-N-methylheptanamide, hydrochloride

Yield 22.4%

Solvents

dimethyl sulfoxide

Conditions

Workup

1. 1
   TemperatureThe reaction mixture was heated at 145° overnight under nitrogen
2. 2
   Extractionextracted with ether
3. 3
   WashThe ether layer was washed with 1N HCL
4. 4
   Otherto give unreacted
5. 5
   Extractionit was extracted with ether
6. 6
   WashThe organic layer was washed with water and saturated sodium chloride
7. 7
   Dryingdried over anhydrous magnesium sulfate
8. 8
   Concentrationconcentrated under vacuum
9. 9
   workup.ADDITIONThe residue was treated with HCl in ether

Procedure

To a solution of N-[4,4-bis(trifluoromethyl)-2-(4-fluorophenyl)-4,5-dihydro-1H-imidazol-5-yl]-N-methylheptanamide hydrochloride (0.20 g, 0.4 mmole) in dimethyl sulfoxide (5 mL) was added potassium carbonate (0.29 g, 1.2 mmole) and piperidine (0.10 g, 1.2 mmole). The reaction mixture was heated at 145° overnight under nitrogen. The solution was cooled to room temperature, poured into water and extracted with ether. The ether layer was washed with 1N HCL to give unreacted starting material. The aqueous layer was made basic and it was extracted with ether. The organic layer was washed with water and saturated sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under vacuum. The residue was treated with HCl in ether to give the title compound (50 mg, 22%) as a semi solid: MS m/e 521 (M+ +H); 1H NMR (CDCl3 /TMS) δ 0.90(m,3H,CH3), 1.30(m,8H,(CH2)4), 1.67(m,6H,(CH2)3), 2.40(t,2H,CH2), 2.90(s,3H,NCH3), 2.97(s,3H,NCH3), 3.30(m,4H,2CH2), 6.53(s,1H,CH), 6.90(d,2H,Harom), 7.53(d,2H,Harom).

Source