Dimethylformamide → 3-Amino-5-(trifluoromethyl)pyridine-2-carbonitrile

HRID 1775270Notes

Reaction equation

[NH2:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH3:13][N:14](C=O)C.C(OCC)(=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[NH2:1][C:2]1[C:3]([C:13]#[N:14])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 5.14 g of 3-amino-2-chloro-5-trifluoromethylpyridine, 3.92 g of zinc cyanide, 1.19 g of tris(dibenzylideneacetone)dipalladium(0), 1.45 g of 1,1′-bis(diphenylphosphino)ferrocene and 20 ml of DMF was stirred at 150° C. for 40 minutes. Ethyl acetate and water were added to the cooled reaction mixture, and the mixture was filtered. The aqueous layer of the filtrate was extracted with ethyl acetate, then combined with the organic layer of the filtrate and washed with water, and dried over anhydrous magnesium sulfate. The mixture was concentrated under reduced pressure, and then the resulting residue was applied to a silica gel column chromatography to obtain 2.23 g of 3-amino-2-cyano-5-trifluoromethylpyridine.

Workup

filtrationthe mixture was filtered
extractionThe aqueous layer of the filtrate was extracted with ethyl acetate
washwashed with water
dry with materialdried over anhydrous magnesium sulfate
concentrationThe mixture was concentrated under reduced pressure

Sources & evidence

ORD record: ord-d4aa2b84fb7b4aea933d1f76df081531
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260436B2

Reaction notes

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