Dimethylacetamide → 5-Chloro-3-methylpyridine-2-carbonitrile

HRID 1526553Notes

Reaction equation

Br[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([Cl:9])=[CH:4][N:3]=1.C[C:11]([N:13](C)C)=O>O.[C-]#N.[Zn+2].[C-]#N.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.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]>[Cl:9][C:5]1[CH:6]=[C:7]([CH3:8])[C:2]([C:11]#[N:13])=[N:3][CH:4]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 2-bromo-5-chloro-3-methylpyridine (45 g, 218 mmol), zinc cyanide (8.30 mL, 131 mmol), tris(dibenzylideneacetone) dipalladium (0) (4.99 g, 5.45 mmol), and 1,1′-bis(diphenylphosphino)ferrocene (6.04 g, 10.90 mmol) in dimethylacetamide (40 mL) was heated to 110° C. for 4 hours. The reaction mixture was cooled to RT, diluted with water and extracted with ethyl acetate. The organic phase obtained was concentrated under reduced pressure and residue purified by chromatography on silica gel using ISCO eluting with 0-60% EtOAc/hex to afford the title compound 5-chloro-3-methylpicolinonitrile (25.4 g, 166 mmol, 76% yield). LC/MS (ESI+) m/z=153.1 (M+H).

Workup

temperatureThe reaction mixture was cooled to RT
extractionextracted with ethyl acetate
customThe organic phase obtained
concentrationwas concentrated under reduced pressure and residue
custompurified by chromatography on silica gel using ISCO
washeluting with 0-60% EtOAc/hex

Sources & evidence

ORD record: ord-9859ff9bf0924feea8a4f8097b05ea35
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085576B2

Reaction notes

Loading…