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

HRID 886104Notes

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 (1H, s), 6.90 (1H, s), 4.01 (3H, 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-1a0f934d5d4242cc8f73e5837833592c
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08242104B2

Reaction notes

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