Acetyl chloride → 1-(2,3-Dihydro-5-benzofuranyl)ethanone

HRID 1669141Notes

Reaction equation

HRID 1669141 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].[C:5](Cl)([CH3:7])=[O:6].[O:9]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[CH2:11][CH2:10]1>C(Cl)Cl>[O:9]1[C:13]2[CH:14]=[CH:15][C:16]([C:5](=[O:6])[CH3:7])=[CH:17][C:12]=2[CH2:11][CH2:10]1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 10329DihydrobenzofuranHCID 6451240Aluminum(III) Chloride

Product 1

HCID 1452201-(2,3-Dihydro-5-benzofuranyl)ethanoneYield 94.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

AlCl3 (12.4 g, 93.0 mmol) was added in small portions to a stirred solution of AcCl (12.6 mL, 177.7 mmol) in dry DCM (100 mL) at −10° C. and the mixture stirred until homogeneous (15 min). The solution was added, via a cannula, to a stirred solution of 2,3-dihydro-1-benzofuran (190) (11.2 g, 93.0 mmol) in dry DCM (100 mL) at −10° C. and the solution stirred for 30 min at −10° C., and then poured into ice/cHCl (5:1 v/v, 1 L). The mixture was stirred for 2 h, extracted with DCM (3×100 mL), the combined organic fraction dried, and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (10-20%) of EtOAc/pet. ether, to give ketone 191 (14.23 g, 94%) as a white solid: mp 59-60° C. [lit. (Dun, J. P., et al., J. Med. Chem. 1986, 29, 2326-2329.) mp 60° C.]; 1H NMR δ 7.85 (d, J=1.9 Hz, 1H, H-4), 7.79 (dd, J=8.5, 1.9 Hz, 1H, H-6), 6.80 (d, J=8.5 Hz, 1H, H-7), 4.65 (t, J=8.7 Hz, 2H, H-2), 3.18 (br t, J=8.7 Hz, 2H, H-3), 2.13 (s, 3H, CH3).

Workup

  1. stirringthe solution stirred for 30 min at −10° C.
  2. stirringThe mixture was stirred for 2 h
  3. extractionextracted with DCM (3×100 mL)
  4. customthe combined organic fraction dried
  5. customthe solvent evaporated
  6. customThe residue was purified by chromatography
  7. washeluting with a gradient (10-20%) of EtOAc/pet. ether

Sources & evidence

ORD record
ord-91929c8abbad408692e4d14ab448472f
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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