Methanol → Methyl 5-cyano-2-methylbenzoate

HRID 1348908

Reaction equation

HRID 1348908 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[C:5]#[N:6].[C:11](=[O:14])([O-])[O-:12].[Li+].[Li+].[CH3:17]O>Cl[Pd]Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[C:5]([C:4]1[CH:7]=[CH:8][C:9]([CH3:10])=[C:2]([CH:3]=1)[C:11]([O:12][CH3:17])=[O:14])#[N:6]

Participants

6

Reactant 3

HCID 887MethanolHCID 11125Lithium CarbonateHCID 888943-Chloro-p-toluonitrile

Product 1

HCID 9989736Methyl 5-cyano-2-methylbenzoateYield 50%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
140 °C

Procedure

A solution of 3-chloro-4-methylbenzonitrile (25.0 g, 0.165 mol) in methanol (250 mL) in a steel reaction vessel was treated with lithium carbonate (13.4 g, 0.182 mol) and PdCl2.dppf (6.75 g). The vessel was purged with nitrogen, sealed, and heated to 140° C. at 400 psi for 17 hours, filtered and concentrated. The concentrate was treated with ethyl acetate, washed with saturated NaHCO3, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash chromatography on silica gel with 95:5 to 85:15 hexanes/ethyl acetate to provide 14.4 g (50%) of the desired product. MS (DCI/NH3) m/z 193.0 (M+NH4)+; 1H NMR (CDCl3) δ 8.22 (d, 1H), 7.67 (dd, 1H), 7.37 (d, 1H), 3.93 (s, 3H), 2.68 (s, 3H).

Workup

  1. customThe vessel was purged with nitrogen
  2. customsealed
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionThe concentrate was treated with ethyl acetate
  6. washwashed with saturated NaHCO3
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe concentrate was purified by flash chromatography on silica gel with 95:5 to 85:15 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-6cd35102c56348cbbb0f024b5472186a
Source dataset
uspto-grants-2007_05
Patent number
US07211595B2

Linked notes

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