Water → Methyl 5-cyano-2-(trifluoromethyl)benzoate

HRID 241438Notes

Reaction equation

HRID 241438 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([C:12]([F:15])([F:14])[F:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].O.CCOC(C)=O.C[C:24]([N:26](C)C)=O>[C-]#N.[Zn+2].[C-]#N.[Zn].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.[Pd+2].[Pd+2].C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2]>[C:24]([C:2]1[CH:3]=[CH:4][C:5]([C:12]([F:15])([F:14])[F:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8])#[N:26]

Participants

9

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 31374DimethylacetamideHCID 463111105-Chloro-2-(trifluoromethyl)benzoic acid methyl ester

Product 1

HCID 71060125Methyl 5-cyano-2-(trifluoromethyl)benzoateYield 66.5%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 11170526di-palladium (II) tris(dibenzylideneacetone)CatalystHCID 15826098Cyclopenta-1,3-diene;cyclopenta-2,4-dien-1-yl(diphenyl)phosphane;iron(2+)Catalyst

Conditions

Temperature
85 °C

Procedure

Dissolve methyl 5-chloro-2-(trifluoromethyl)benzoate (500 mg, 2.1 mmol), zinc (II) cyanide (197 mg, 1.68 mmol), zinc (55 mg, 0.84 mmol), di-palladium (II) tris(dibenzylideneacetone) (192 mg, 0.21 mmol), and diphenylphosphino ferrocene (233 mg, 0.42 mmol) in dimethylacetamide (20 mL). Heat the reaction mixture to 85° C., and stir for 12 hours. Pour the resulting mixture into water, and extract with EtOAc (2×100 mL). Dry the combined organics over sodium sulfate; filter; collect the filtrate; and concentrate the filtrate under reduced pressure. Purify the residue by silica gel chromatography eluting with 50:1 petroleum ether:EtOAc to give the title compound (320 mg, 66.5% yield) as a white solid. 1H NMR (300 MHz, CDCl3,) δ 8.09 (s, 1H), 7.90 (s, 2H), 3.80 (s, 3H).

Workup

  1. extractionextract with EtOAc (2×100 mL)
  2. dry with materialDry the combined organics over sodium sulfate
  3. filtrationfilter
  4. customcollect the filtrate
  5. concentrationand concentrate the filtrate under reduced pressure
  6. customPurify the residue by silica gel chromatography
  7. washeluting with 50:1 petroleum ether

Sources & evidence

ORD record
ord-2311be9f0c484a85a8b17538c4045416
Source dataset
uspto-grants-2014_02
Patent number
US08648200B2

Reaction notes

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