Water → Methyl 3-cyano-4-isopropoxybenzoate

HRID 1820959Notes

Reaction equation

HRID 1820959 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])[C:5]([O:7][CH3:8])=[O:6].O.[CH3:17][N:18](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:17]([C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])[C:5]([O:7][CH3:8])=[O:6])#[N:18]

Participants

6

Reactant 3

HCID 962WaterHCID 6228DimethylformamideHCID 21956810Methyl 3-bromo-4-isopropoxybenzoate

Product 1

HCID 21956805Methyl 3-cyano-4-isopropoxybenzoate

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
120 °C

Procedure

A mixture of 1.32 g (4.83 mmol) of methyl 3-bromo-4-isopropyloxybenzoate (from Step B), 341 mg (2.90 mmol) of zinc cyanide, 67 mg (0.12 mmol) of 1,1′-bis(diphenylphosphino)ferrocene, 44 mg (0.05 mmol) of tris(dibenzylideneacetone) dipalladium(0)-chloroform complex and 50 μL of H2O in 5.0 mL of DMF was stirred at 120° C. for 48 h. The mixture was cooled, then partitioned between EtOAc and sat'd NaCl. The aqueous layer was separated and extracted with 3× EtOAc. The organic layers were combined, dried over MgSO4 and concentrated. Chromatography on a Biotage 40M cartridge using 9:1 v/v hexanes/EtOAc gave 802 mg of the title compound: 1H NMR (500 MHz, CDCl3) δ 1.44 (d, J=6.2, 6H), 3.91 (s, 3H), 4.71-4.79 (m, 1H), 6.99 (d, J=8.9, 1H), 8.18 (dd, J=2.2, 8.8, 1H), 8.24 (d, J=2.1, 1H).

Workup

  1. temperatureThe mixture was cooled
  2. custompartitioned between EtOAc
  3. customThe aqueous layer was separated
  4. extractionextracted with 3× EtOAc
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-6fe4c2ce5bce46fb964064ddeaa8ee1b
Source dataset
uspto-grants-2009_10
Patent number
US07605171B2

Reaction notes

Loading…