Triethylamine → 1-[6-{3-[3,5-Bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl}-2-(trifluoromethyl)pyridin-3-yl]methanamine

HRID 2206923Notes

Reaction equation

HRID 2206923 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C:13]2([C:30]([F:33])([F:32])[F:31])[CH2:17][CH2:16][N:15]([C:18]3[N:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[C:21]([CH2:28]O)=[CH:20][CH:19]=3)[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C([N:38](CC)CC)C.CS(Cl)(=O)=O.O.N>C(#N)C>[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C:13]2([C:30]([F:33])([F:32])[F:31])[CH2:17][CH2:16][N:15]([C:18]3[N:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[C:21]([CH2:28][NH2:38])=[CH:20][CH:19]=3)[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 12896473Azane;hydrateHCID 87160620[6-{3-[3,5-Bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl}-2-(trifluoromethyl)pyridin-3-yl]methanol

Product 1

HCID 871585361-[6-{3-[3,5-Bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl}-2-(trifluoromethyl)pyridin-3-yl]methanamineYield 64.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Procedure

[6-{3-[3,5-Bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl}-2-(trifluoromethyl)pyridin-3-yl]methanol (1.55 g) and triethylamine (0.4 g) were added to acetonitrile (30 ml), and an acetonitrile solution (10 ml) of methanesulfonyl chloride (0.4 g) was added dropwise thereto under ice cooling. Upon the completion of the dropwise addition, the reaction liquid was stirred at room temperature for 1 hour, and then the resulting solution was added dropwise to a mixture solution containing 28% ammonia water (30 ml) and acetonitrile (50 ml), which had been prepared separately, under ice cooling. After stirring at room temperature for 12 hours, the reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure and the purified by silica gel chromatography to obtain 1-[6-{3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl}-2-(trifluoromethyl)pyridin-3-yl]methanamine (1.0 g).

Workup

  1. additionUpon the completion of the dropwise addition
  2. customthe reaction liquid
  3. additionthe resulting solution was added dropwise to a mixture solution
  4. customhad been prepared separately, under ice cooling
  5. stirringAfter stirring at room temperature for 12 hours
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customthe purified by silica gel chromatography

Sources & evidence

ORD record
ord-669311fdae7e41e08cd9b878438c319c
Source dataset
uspto-grants-2016_06
Patent number
US09375000B2

Reaction notes

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