Ethanol → Ethyl 5-methoxy-2,3,4-trifluorobenzoate

HRID 10275Notes

Reaction equation

HRID 10275 reaction equation
[F:1][C:2]1[C:10]([F:11])=[C:9]([F:12])[C:8]([O:13][CH3:14])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:15](Cl)(=O)[C:16](Cl)=O.C(O)C.C([O-])(O)=O.[Na+]>ClCCl.CN(C)C=O>[CH2:15]([O:5][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([O:13][CH3:14])[C:9]([F:12])=[C:10]([F:11])[C:2]=1[F:1])[CH3:16]

Participants

7

Reactant 4

HCID 702EthanolHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 219792032,3,4-Trifluoro-5-methoxybenzoic acid

Product 1

HCID 21041176Ethyl 5-methoxy-2,3,4-trifluorobenzoateYield 96.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 2,3,4-trifluoro-5-methoxybenzoic acid (Hayashi et al., Bull. Chem. Soc. Jap., 1972; 45(9):2909–2914, 3.443 g, 16.7 mmol) in dichloromethane (100 mL) at 0° C. is treated with oxalyl chloride (7 mL, 80 mmol) followed by N,N-dimethylformamide (4 drops). The mixture is stirred at room temperature for 3.5 hours, concentrated to near dryness, and co-evaporated with benzene. The acid chloride is then diluted with dichloromethane, cooled to 0° C., and treated with absolute ethanol (10 mL, 170 mmol). The resulting solution is stirred at room temperature for 20 hours, poured into saturated NaHCO3 solution, and extracted with dichloromethane. The organic extracts are washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum to afford the title compound (3.785 g). 1H NMR (200 MHz, CDCl3): δ 7.36–7.29 (m, 1H), 4.42 (q, 2H), 3.93 (s, 3H), 1.44 (t, 3H).

Workup

  1. concentrationconcentrated
  2. additionThe acid chloride is then diluted with dichloromethane
  3. temperaturecooled to 0° C.
  4. stirringThe resulting solution is stirred at room temperature for 20 hours
  5. extractionextracted with dichloromethane
  6. washThe organic extracts are washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-49a5979b87634687b079fe6f0767adec
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Reaction notes

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