Dimethylformamide → 4-Chloro-6-methoxypyridine-3-carbonitrile

HRID 1629131Notes

Reaction equation

[Cl:1][C:2]1[C:7](I)=[CH:6][N:5]=[C:4]([O:9][CH3:10])[CH:3]=1.[CH3:11][N:12](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[C:7]([C:11]#[N:12])=[CH:6][N:5]=[C:4]([O:9][CH3:10])[CH:3]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A suspension of 4-chloro-5-iodo-2-methoxy-pyridine (30.5 g, 0.11 mol), zinc (II) cyanide (7.97 g, 68 mmol), Pd(PPh3)4 (6.56 g, 5.66 mmol) and DMF (450 mL) was degassed and then heated at 120° C. for 1 h before being concentrated in vacuo. The resultant residue was treated with water then extracted with DCM, the organic extract dried (MgSO4), filtered, then concentrated in vacuo. The resultant residue was crystallized from DCM to give the title compound (10.1 g, 54%). The mother liquors were concentrated in vacuo and the residue subjected to flash chromatography (SiO2 gradient 0 to 100% ethyl acetate in cyclohexane) then crystallization from cyclohexane to give the further title compound (5.16 g, 28%, 82% total). 1H NMR 400 MHz (CDCl3) δ: 8.45 (1 H, s), 6.90 (1 H, s), 4.01 (3 H, s).

Workup

customwas degassed
concentrationbefore being concentrated in vacuo
additionThe resultant residue was treated with water
extractionthen extracted with DCM
extractionthe organic extract
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe resultant residue was crystallized from DCM

Sources & evidence

ORD record: ord-0d21065f27cd4009abb0ff9e2f542f63
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785626B2

Reaction notes

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