Dimethylformamide → 1-(6-Chloro-4-methoxy-2-benzofuranyl)ethanone

HRID 625121Notes

Reaction equation

HRID 625121 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[C:5]([CH:6]=O)=[C:4]([OH:12])[CH:3]=1.CN(C)C=O.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:25][C:26](=[O:28])[CH3:27]>>[Cl:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[C:5]2[CH:6]=[C:25]([C:26](=[O:28])[CH3:27])[O:12][C:4]=2[CH:3]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6571ChloroacetoneHCID 10796Cesium carbonateHCID 86700905HCID 86700905, compound

Product 1

HCID 867009061-(6-Chloro-4-methoxy-2-benzofuranyl)ethanoneYield 66.4%

Conditions

Temperature
65 °C

Procedure

A stirred solution of 4-chloro-2-hydroxy-6-methoxybenzaldehyde (Example 37B, 1.79 g, 9.59 mmol) in N,N-dimethylformamide (15 mL, 9.59 mmol) was charged with cesium carbonate (3.75 g, 11.51 mmol) and 1-chloropropan-2-one (0.975 mL, 11.51 mmol). The reaction mixture was heated in a sealable vessel at 65° C. for 7 hours, was filtered over a Whatman filter paper to remove insolubles rinsing with DCM then washed with sat. NaHCO3. The organic phase was dried (MgSO4), filtered and concentrated to dryness. The residue was purified by ISCO using hexanes/EtOAc as eluent. Fractions containing the desired product were concentrated to give the title material (1.43 g, 6.37 mmol, 66% yield) as a light yellow solid. LC (Method A): 1.952 min. LCMS (APCI) calcd for C11H10ClO3 [M+H]+ m/z 225.03, found 225.0. 1H NMR (CDCl3, 400 MHz) δ ppm: 7.94 (d, J=0.8 Hz, 1H), 7.49 (dd, J=0.8, 1.6 Hz, 1H), 6.97 (d, J=1.6 Hz, 1H), 3.97 (s, 3H).

Workup

  1. filtrationwas filtered over a Whatman
  2. filtrationfilter paper
  3. customto remove insolubles
  4. washrinsing with DCM
  5. washthen washed with sat. NaHCO3
  6. dry with materialThe organic phase was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe residue was purified by ISCO
  10. additionFractions containing the desired product
  11. concentrationwere concentrated

Sources & evidence

ORD record
ord-7e0fcef2cfad4eb38c43b4f9d85ed955
Source dataset
uspto-grants-2016_04
Patent number
US09303065B2

Reaction notes

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