Dimethylformamide → Methyl 4-cyano-3-hydroxybenzoate

HRID 1871191Notes

Reaction equation

HRID 1871191 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1I)[C:5]([O:7][CH3:8])=[O:6].CCOC(C)=O.O.[CH3:20][N:21](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>[C:20]([C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=1[OH:1])#[N:21]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 10378812Methyl 3-hydroxy-4-iodobenzoateHCID 22728543Water ethylacetate

Product 1

HCID 16641129Methyl 4-cyano-3-hydroxybenzoateYield 76%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

A mixture of the iodide product from Step B (101 g, 0.36 mol) and zinc(II)cyanide (30 g, 0.25 mol) in 400 mL of dry DMF was degassed by bubbling argon through the solution for 20 minutes. Tetrakis(triphenylphosphine)palladium (8.5 g, 7.2 mmol) was added, and the solution was heated to 80° C. for 4 hours. The solution was cooled to room temperature, then stirred for an additional 36 hours. The reaction was poured into EtOAc/water, and the organic layer was washed with brine (4x), dried (Na2SO4), and concentrated in vacuo to provide the crude product. Purification by column chromatography through silica gel (30%-50% EtOAc/hexane) provided the titled product (48.8 g, 76% yield).

Workup

  1. customwas degassed
  2. customby bubbling argon through the solution for 20 minutes
  3. temperatureThe solution was cooled to room temperature
  4. washthe organic layer was washed with brine (4x)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customto provide the crude product
  8. customPurification by column chromatography through silica gel (30%-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-1ab24b46305740fe86357a056a920ec2
Source dataset
uspto-grants-2000_08
Patent number
US06103487

Reaction notes

Loading…