Ethyl Acetate → Methyl 2-cyano-6-methylisonicotinate

HRID 2071151Notes

Reaction equation

Cl[C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH3:12])[N:11]=1)[C:5]([O:7][CH3:8])=O.[CH3:13]COC(C)=O.[NH4+:19].[OH-:20]>CN(C=O)C.[C-]#N.[C-]#N.[Zn+2].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>[C:13]([C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH3:12])[N:11]=1)[C:5]([O:7][CH3:8])=[O:20])#[N:19]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 2.03 g (11 mmol) of methyl 2-chloro-6-methylisonicotinate (Aldrich) in 20 mL of DMF (degassed) was added 1.14 g (9.73 mmol) of Zn(CN)2 and 1.18 g (1.02 mmol) of Pd(PPh3)4. The mixture was stirred at 80° C. for 12.5 h, and EtOAc and 20 mL of 10% NH4OH aqueous solution were added. The organic layer was washed with 20 mL of 10% NH4OH and 20 mL of brine. The combined aqueous layers were reextracted with EtOAc and washed with brine. The combined extracts were dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (30% EtOAc/hexanes) provided 1.3 g of methyl 2-cyano-6-methylisonicotinate in 68% yield.

Workup

washThe organic layer was washed with 20 mL of 10% NH4OH and 20 mL of brine
washwashed with brine
dry with materialThe combined extracts were dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customPurification by flash silica gel chromatography (30% EtOAc/hexanes)

Sources & evidence

ORD record: ord-11532bef617c47be9faf70fd496de537
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299267B2

Reaction notes

Loading…