Dimethylformamide → 3-Chloro-5-hydroxypicolinonitrile

HRID 221798Notes

Reaction equation

HRID 221798 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:9]C(=O)C)[CH:5]=[N:6][C:7]=1Cl.[CH3:13][N:14](C=O)C>CC(OC)(C)C.O.[Ar].[Zn].[C-]#N.[C-]#N.[Zn+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].Cl[Pd]Cl>[Cl:1][C:2]1[C:7]([C:13]#[N:14])=[N:6][CH:5]=[C:4]([OH:9])[CH:3]=1

Participants

8

Reactant 2

HCID 6228DimethylformamideHCID 145952225,6-Dichloropyridin-3-yl acetate

Product 1

HCID 666654733-Chloro-5-hydroxypicolinonitrile

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 85978949argon ZnCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of acetic acid 5,6-dichloro-pyridin-3-yl ester (CA 110861-18-2, Synthesis, 1990, 499) (4.88 g, 23.6 mmol) in anhydrous DMF (45 ml) was added after degasing with argon Zn-dust (70 mg, 1.07 mmol), Zn(CN)2 (1.28 g, 10.9 mmol) and DPPF PdCl2 (966 mg, 1.18 mmol) and the reaction mixture was heated for 6 h at 130° C. and 18 h at 150° C. The reaction mixture was diluted with TBME and H2O, filtered over Celite, and the product was extracted with TBME. Combined extracts were washed with water and brine, dried over MgSO4, filtered and concentrated. The title compound was obtained as a beige solid after crystallization from EtOAc-hexane: TLC(CH2Cl2-MeOH 19:1): Rf=0.22;

Workup

  1. filtrationfiltered over Celite
  2. extractionthe product was extracted with TBME
  3. washCombined extracts were washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-73c6c07de58346f880298eee000aa0f6
Source dataset
uspto-grants-2012_06
Patent number
US08207164B2

Reaction notes

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