Benzyl(methoxymethyl)((trimethylsilyl)methyl)amine → 4-[1-Benzyl-3-(trifluoromethyl)pyrrolidin-3-yl]-2,6-bis(trifluoromethyl)pyridine

HRID 1500195Notes

Reaction equation

HRID 1500195 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[C:7]([C:9]([C:11]([F:14])([F:13])[F:12])=[CH2:10])[CH:6]=[C:5]([C:15]([F:18])([F:17])[F:16])[N:4]=1.[CH2:21]([N:28]([CH2:32][Si](C)(C)C)[CH2:29]OC)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>ClCCl.FC(F)(F)C(O)=O>[CH2:21]([N:28]1[CH2:32][CH2:10][C:9]([C:7]2[CH:8]=[C:3]([C:2]([F:1])([F:19])[F:20])[N:4]=[C:5]([C:15]([F:18])([F:16])[F:17])[CH:6]=2)([C:11]([F:14])([F:13])[F:12])[CH2:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 2

HCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 866646212,6-Bis(trifluoromethyl)-4-(3,3,3-trifluoroprop-1-en-2-yl)pyridine

Product 1

HCID 866749264-[1-Benzyl-3-(trifluoromethyl)pyrrolidin-3-yl]-2,6-bis(trifluoromethyl)pyridineYield 85%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidCatalystHCID 6344DichloromethaneSolvent2×

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 removed under 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).

Workup

  1. temperaturewhile cooling with ice
  2. additionOn completion of the dropwise addition
  3. washThe mixture was washed with saturated sodium bicarbonate water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationAfter the drying agent was filtered off
  6. customthe solvent was removed under reduced pressure
  7. customthe residue was then purified by silica gel chromatography

Sources & evidence

ORD record
ord-9a6e225efbe74365bce90a537d0b3117
Source dataset
uspto-grants-2015_12
Patent number
US09206122B2

Reaction notes

Loading…