Dimethylformamide → Methyl 4-cyano-2-fluorobenzoate

HRID 2410521Notes

Reaction equation

HRID 2410521 reaction equation
C(Cl)(=O)C(Cl)=O.CN([CH:10]=[O:11])C.[C:12]([C:14]1[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[C:16]([F:23])[CH:15]=1)#[N:13].C(N(CC)CC)C>C(Cl)Cl.Cl.CO>[C:12]([C:14]1[CH:22]=[CH:21][C:17]([C:18]([O:11][CH3:10])=[O:19])=[C:16]([F:23])[CH:15]=1)#[N:13]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 5906594-Cyano-2-fluorobenzoic acid

Product 1

HCID 15278726Methyl 4-cyano-2-fluorobenzoate

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (9.0 mL, 106.6 mmol) and DMF (0.5 mL) were added into a suspension of 4-cyano-2-fluorobenzoic acid (ABCR, 16 g, 96.9 mmol) in anhydrous DCM (300 mL) The resulting mixture was stirred at RT, and then evaporated under reduced pressure. The residue was taken up with anhydrous THF (150 mL) and added dropwise into a solution of methanol (50 mL) and triethylamine (25.8 mL, 193.8 mmol) at 4° C. The reaction mixture was diluted with a 0.1N aqueous solution of HCl (200 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with a semi-saturated aqueous solution of NaHCO3 (200 mL) and water (200 mL), dried (MgSO4) and concentrated under vacuum to give the title compound as a pale yellow solid (17.8 g, quantitative). HPLC (Method A) Rt 2.81 min (Purity: 93.9%).

Workup

  1. customevaporated under reduced pressure
  2. extractionextracted with EtOAc (3×100 mL)
  3. washThe combined organic layers were washed with a semi-saturated aqueous solution of NaHCO3 (200 mL) and water (200 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-5c68f3ab01d941c184ac14f70e88ded6
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Reaction notes

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