Ammonia → (1-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)cyclopropyl)methanamine

HRID 578858Notes

Reaction equation

HRID 578858 reaction equation
[Cl:1][C:2]1[C:3]([C:12]2([C:15]#[N:16])[CH2:14][CH2:13]2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.N.[H][H]>CO.[Ni]>[Cl:1][C:2]1[C:3]([C:12]2([CH2:15][NH2:16])[CH2:14][CH2:13]2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 715592781-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)cyclopropane-1-carbonitrileHCID 178418361HCID 178418361, compound2×

Product 1

HCID 71559141(1-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)cyclopropyl)methanamineYield 92.6%

Reagents, catalysts & solvents 2

HCID 935NickelCatalyst2×HCID 887MethanolSolvent

Procedure

10 g of 1-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-cyclopropanecarbonitrile (step 1 of preparation example 1) was dissolved in 200 ml of methanol and 50 ml of ammonia (7N solution in methanol) was added, followed by 3 g of Raney Nickel. The reactor was sealed and the reaction mixture was stirred under 3 bar of hydrogen at ambient temperature for 2 hours. Then additional 5 g of Raney Nickel were added and the reaction mixture was stirred under 3 bar of hydrogen at ambient temperature for another 15 hours. Then the reaction mixture was filtered over celite and the filtrate was concentrated. Thus, 9.41 g of crude C-[1-(3-chloro-5-trifluoromethyl-pyridin-2-yl)-cyclopropyl]-methylamine was obtained as an orange oil, which was used for the next step without further purification. 1H-NMR (CDCl3): 8.72 ppm (s, 1H), 7.90 ppm (s, 1H), 3.00 ppm (s, 2H), 1.10 ppm (s, 2H, broad), 1.00 ppm (m, 2H), 0.90 ppm (m, 2H).

Workup

  1. customThe reactor was sealed
  2. filtrationThen the reaction mixture was filtered over celite
  3. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-c001b19179a742b1bd97defda8beeba7
Source dataset
uspto-grants-2015_05
Patent number
US09040708B2

Reaction notes

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