Dimethylformamide → 3-Chloro-5-(methoxymethyl)picolinonitrile

HRID 2196373Notes

Reaction equation

HRID 2196373 reaction equation
Cl[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([CH2:9][O:10][CH3:11])=[CH:4][N:3]=1.[CH3:12][N:13](C=O)C>[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:8][C:7]1[C:2]([C:12]#[N:13])=[N:3][CH:4]=[C:5]([CH2:9][O:10][CH3:11])[CH:6]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 111379602,3-Dichloro-5-(methoxymethyl)pyridine

Product 1

HCID 666655543-Chloro-5-(methoxymethyl)picolinonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 85978949argon ZnCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
145 °C

Procedure

To a solution of 2,3-dichloro-5-methoxymethyl-pyridine (CA registry 202395-72-0) (7.5 g, 38 mmol) in DMF (100 ml) was added after degasing with argon Zn-dust (126 mg, 1.91 mmol), Zn(CN)2 (2.27 g, 19.1 mmol) and DPPF PdCl2 (0.997 g, 1.15 mmol) and the reaction mixture was heated for 2 h at 145° C. The reaction mixture was concentrated, the residue redissolved in TBME and 5% aqueous NaHCO3 solution and extracted with TBME. Combined extracts were washed with water and brine, dried over MgSO4, filtered and concentrated. The title compound was obtained after chromatography on silica gel (hexane-EtOAc 20:1 to EtOAc) as beige crystals: TLC (hexane-EtOAc 1:1): Rf=0.47;

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue redissolved in TBME
  3. extraction5% aqueous NaHCO3 solution and extracted with TBME
  4. washCombined extracts were washed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-bd89e88de253464bb2280ebfd83bf391
Source dataset
uspto-grants-2012_12
Patent number
US08338413B1

Reaction notes

Loading…