Dimethylformamide → Methyl 2-chloro-4-cyanobenzoate

HRID 2404312Notes

Reaction equation

HRID 2404312 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[C:23]([Cl:31])[CH:22]=1.[CH3:32][N:33](C=O)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[C-]#N.[Zn+2].[C-]#N>[Cl:31][C:23]1[CH:22]=[C:21]([C:32]#[N:33])[CH:30]=[CH:29][C:24]=1[C:25]([O:27][CH3:28])=[O:26]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 11776TriphenylphosphineHCID 22058730Methyl 4-Bromo-2-chlorobenzoate

Product 1

HCID 53845357Methyl 2-chloro-4-cyanobenzoate

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 167845palladium(II) acetateCatalyst

Procedure

A mixture of triphenylphosphine polymer bound (239 mg, 0.72 mmol) and palladium(II) acetate (75 mg, 0.33 mmol) was prepared in DMF (12 mL) under nitrogen atmosphere and stirred at RT for 2 hours. Zinc cyanide (561 mg, 4.77 mmol) and methyl 4-bromo-2-chlorobenzoate (1.19 g, 4.77 mmol) were added and the resulting mixture was heated under microwave irradiation at 140° C. for 50 minutes. The reaction mixture was filtered and the resin was washed with Et2O (3×10 mL). The combined organic layers were washed with water (3×5 mL) and brine (10 mL), dried (MgSO4) and concentrated under vacuum to give the title compound as a white powder. 1H NMR (DMSO-d6, 300 MHz) δ 8.23 (m, 1H), 7.96 (m, 2H), 3.90 (s, 3H). HPLC (Method A) Rt 3.39 min (Purity: 97.6%).

Workup

  1. temperaturethe resulting mixture was heated under microwave irradiation at 140° C. for 50 minutes
  2. filtrationThe reaction mixture was filtered
  3. washthe resin was washed with Et2O (3×10 mL)
  4. washThe combined organic layers were washed with water (3×5 mL) and brine (10 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-6cfbda45fb6341f299433bdb1444298e
Source dataset
uspto-grants-2014_08
Patent number
US08802704B2

Reaction notes

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