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

HRID 1096557
Notes
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Reaction equation

HRID 1096557 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: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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

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 1

HCID 6342AcetonitrileSolvent

Procedure

At 45° C., 520 mg (2.89 mmol) of 6-chloro-3-chloromethyl-5-fluoropyridine (Va-4), 1.05 ml (14.44 mmol) of 2,2-difluoroethylamine and 400 μl (2.89 mmol) of triethylamine in 50 ml of acetonitrile are stirred for about 48 hours. During the reaction, after about 16 hours and 32 hours, a further 0.42 ml (5.78 mmol) of 2,2-difluoroethylamine are added in each case. The reaction mixture is concentrated under reduced pressure and then taken up in 1 N aqueous hydrochloric acid and washed with ethyl acetate. The aqueous phase is made alkaline using 2.5 N aqueous sodium hydroxide solution and extracted repeatedly with ethyl acetate. Drying of the combined organic phases over sodium sulphate and concentration under reduced pressure gives 370 mg (57% of theory) of N-[(6-chloro-5-fluoropyridin-3-yl)methyl]-2,2-difluoroethylamine.

Workup

  1. customDuring the reaction
  2. concentrationThe reaction mixture is concentrated under reduced pressure
  3. washwashed with ethyl acetate
  4. extractionextracted repeatedly with ethyl acetate
  5. dry with materialDrying of the combined organic phases over sodium sulphate and concentration under reduced pressure

Sources & evidence

ORD record
ord-ec5eefc20c8642a28012a98e91093136
Source dataset
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08138350B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes