Ethyl chloroacetate → Ethyl 4-chlorobenzofuran-2-carboxylate

HRID 1471670Notes

Reaction equation

HRID 1471670 reaction equation
Cl[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[Cl:8][C:9]1[CH:16]=[CH:15][CH:14]=[C:13]([OH:17])[C:10]=1[CH:11]=O.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:8][C:9]1[C:10]2[CH:11]=[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[O:17][C:13]=2[CH:14]=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 7751Ethyl chloroacetateHCID 11430Potassium CarbonateHCID 5283932-Chloro-6-hydroxybenzaldehyde

Product 1

HCID 67983046Ethyl 4-chlorobenzofuran-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Ethyl chloroacetate (8.0 mL, 1.3 eq.) was added to a mixture of 2-chloro-6-hydroxy-benzaldehyde (Example 1a), 9.0 g, 57 mmol) and potassium carbonate (16.0 g, 114 mmol) in DMF (100 mL) at rt. The reaction mixture was heated at +120° C. for 1.5 h, cooled to room temperature and filtered through a short bed of Celite. The filtrate was acidified to pH 2 with 5 M HCl and the solution was extracted with dichloromethane (2×100 mL). The combined organic extracts was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography by using hexane/ethyl acetate (9/1) as eluent to give the title compound. Yield: 10 g (77%). 1H NMR (400 MHz, CDCl3) δ ppm 1.44 (t, 3H) 4.56 (q, 2H) 7.29-7.32 (m, 1H) 7.35-7.40 (m, 1H) 7.49-7.52 (m, 1H) 7.60 (s, 1H).

Workup

  1. temperatureThe reaction mixture was heated at +120° C. for 1.5 h
  2. filtrationfiltered through a short bed of Celite
  3. extractionthe solution was extracted with dichloromethane (2×100 mL)
  4. washThe combined organic extracts was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-48ab40ca001b4e55a13d2c4e9e940907
Source dataset
uspto-grants-2015_04
Patent number
US09012457B2

Reaction notes

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