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

HRID 221801Notes

Reaction equation

HRID 221801 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-c0a2fcc8b1ac4f87876fa90c954d2b65
Source dataset
uspto-grants-2012_06
Patent number
US08207164B2

Reaction notes

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