Ethyl Acetate → Methyl 3-cyano-4-methylbenzoate

HRID 2071100

Reaction equation

I[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH3:12])[C:5]([O:7][CH3:8])=O.[NH4+:13].[OH-:14].[CH3:15]COC(C)=O>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:15]([C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH3:12])[C:5]([O:7][CH3:8])=[O:14])#[N:13]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 5.7 g of methyl 3-iodo-4-methylbenzoate in 35 mL of DMF (degassed) was added 1.94 g (16.5 mmol) of Zn(CN)2 and 1.58 g (1.37 mmol) of Pd(PPh3)4. The mixture was stirred at 80° C. in the dark (with the light off) for 6 h. To the mixture was added 50 mL of 10% NH4OH (aq.) and EtOAc. The organic layer was washed with 50 mL of water and 30 mL of brine, and the combined aqueous layers were extracted with EtOAc. The combined extracts were dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (10% EtOAc/hexanes) provided about 3 g of methyl 3-cyano-4-methylbenzoate as a pale yellow solid.

Workup

washThe organic layer was washed with 50 mL of water and 30 mL of brine
extractionthe combined aqueous layers were extracted with EtOAc
dry with materialThe combined extracts were dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customPurification by flash silica gel chromatography (10% EtOAc/hexanes)

Sources & evidence

ORD record: ord-d6bcc60df98349ca9f6d3fb8a358f5a1
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299267B2

Linked notes

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