Water → 3-Chloro-5-fluoromethoxy-pyridine-2-carbonitrile

HRID 1752499Notes

Reaction equation

Cl[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([O:9][CH2:10][F:11])=[CH:4][N:3]=1.O.[CH3:13][N:14](C=O)C>[C-]#N.[Zn+2].[C-]#N.[Zn].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:8][C:7]1[C:2]([C:13]#[N:14])=[N:3][CH:4]=[C:5]([O:9][CH2:10][F:11])[CH:6]=1

Participants

Conditions

Temperature: 145 °C

Procedure

To a solution of 2,3-dichloro-5-fluoromethoxy-pyridine (1.18 g, 6.02 mmol) in dry DMF (14.00 ml) were added Zinc cyanide (0.341 g, 2.90 mmol) and Zinc powder (3.94 mg, 0.060 mmol). The suspension was flushed with Argon (3×). Then tetrakis(triphenylphosphine)palladium(0) (0.570 g, 0.494 mmol) was added. The reaction was heated to 145° C. for 2 h. Water was added and the aqueous layer was extracted twice with Et2O. The combined organic layers were washed with brine, dried with Na2SO4, filtered and evaporated. The residue was purified by chromatography on silica gel (cyclohexane to cyclohexane/EtOAc 7:3) to provide the title compound as yellow oil (515 mg).

Workup

customThe suspension was flushed with Argon (3×)
extractionthe aqueous layer was extracted twice with Et2O
washThe combined organic layers were washed with brine
dry with materialdried with Na2SO4
filtrationfiltered
customevaporated
customThe residue was purified by chromatography on silica gel (cyclohexane to cyclohexane/EtOAc 7:3)

Sources & evidence

ORD record: ord-38ed1b3761594f80b7f77fc4c44e2dc5
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163011B2

Reaction notes

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