Triethylamine → N-[(6-chloro-5-fluoropyridin-3-yl)methyl]-2,2-difluoroethylamine

HRID 659969

Reaction equation

HRID 659969 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8]Cl)=[CH:4][C:3]=1[F:10].[F:11][CH:12]([F:15])[CH2:13][NH2:14].C(N(CC)CC)C>C(#N)C.Cl>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH:14][CH2:13][CH:12]([F:15])[F:11])=[CH:4][C:3]=1[F:10]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 1362742,2-Difluoroethanamine2×HCID 216982012-Chloro-5-(chloromethyl)-3-fluoropyridine

Product 1

HCID 86639346N-[(6-chloro-5-fluoropyridin-3-yl)methyl]-2,2-difluoroethylamineYield 57%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6342AcetonitrileSolvent

Procedure

At 45° C., 520 mg (2.89 mmol) of 6-chloro-3-chloromethyl-5-fluoropyridine (VII-3), 1.05 ml (14.44 mmol) of 2,2-difluoroethylamine and 400 μL (2.89 mmol) of triethylamine are stirred in 50 ml of acetonitrile for about 48 hours. After about 16 and 32 hours, in each case another 0.42 ml (5.78 mmol) of 2,2-difluoroethylamine are added. After concentration of the reaction mixture under reduced pressure, the residue is taken up in 1 N aqueous hydrochloric acid and the mixture is washed with ethyl acetate. The aqueous phase is made alkaline using 2.5 N aqueous sodium hydroxide solution and extracted repeatedly with ethyl acetate. The combined organic phase is dried over sodium sulphate and concentrated under reduced pressure, giving 370 mg (57% of theory) of N-[(6-chloro-5-fluoropyridin-3-yl)methyl]-2,2-difluoroethylamine.

Workup

  1. washthe mixture is washed with ethyl acetate
  2. extractionextracted repeatedly with ethyl acetate
  3. dry with materialThe combined organic phase is dried over sodium sulphate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fd3210e947094643a320aad6d69415e6
Source dataset
uspto-grants-2011_12
Patent number
US08084452B2

Linked notes

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