Reaction #70909

Reaction equation

2,6-bis(trifluoromethyl)-4-(3,3,3-trifluoroprop-1-en-2-yl)pyridine

N-benzyl-1-methoxy-N-[(trimethylsilyl)methyl]methanamine

→

4-[1-benzyl-3-(trifluoromethyl)pyrrolidin-3-yl]-2,6-bis(trifluoromethyl)pyridine

Yield 85.0%

Solvents

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   Temperaturewhile cooling with ice
2. 2
   workup.ADDITIONOn completion of the dropwise addition
3. 3
   WashThe mixture was washed with saturated sodium bicarbonate water
4. 4
   Dryingdried over anhydrous magnesium sulfate
5. 5
   FiltrationAfter the drying agent was filtered off
6. 6
   workup.DISTILLATIONthe solvent was distilled away under the reduced pressure
7. 7
   Otherthe residue was then purified by silica gel chromatography

Procedure

To the solution of 2,6-bis(trifluoromethyl)-4-(3,3,3-trifluoroprop-1-en-2-yl)pyridine (1.25 g) and N-benzyl-1-methoxy-N-[(trimethylsilyl)methyl]methanamine (5.0 g) in dichloromethane was added dropwise the solution of trifluoroacetic acid (0.038 g) in dichloromethane while cooling with ice. On completion of the dropwise addition, the mixture was warmed to room temperature and stirred over night. The mixture was washed with saturated sodium bicarbonate water and dried over anhydrous magnesium sulfate. After the drying agent was filtered off, the solvent was distilled away under the reduced pressure, and the residue was then purified by silica gel chromatography to yield 4-[1-benzyl-3-(trifluoromethyl)pyrrolidin-3-yl]-2,6-bis(trifluoromethyl)pyridine (1.52 g). 1H-NMR (CDCl3) δ: 2.23-2.29 (1H, m), 2.65-2.69 (2H, m), 2.96 (1H, d), 3.05-3.15 (2H, m), 3.58 (1H, d), 3.82 (1H, d), 7.26-7.37 (5H, m), 8.00 (2H, s).

Source