Acetic Acid → 5-Acetylamino-2,3-dihydrobenzofuran

HRID 1669143Notes

Reaction equation

HRID 1669143 reaction equation
Cl.O1C2C=C[C:9]([C:11](=[N:13]O)[CH3:12])=[CH:10]C=2CC1.[CH3:15][C:16]([O:18][C:19]([CH3:21])=O)=O.[CH3:22][C:23](O)=[O:24]>>[O:18]1[C:19]2[CH:21]=[CH:12][C:11]([NH:13][C:23](=[O:24])[CH3:22])=[CH:9][C:10]=2[CH2:15][CH2:16]1

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 7918Acetic AnhydrideHCID 28214741-(2,3-Dihydro-1-benzofuran-5-yl)ethanone oxime

Product 1

HCID 129085765-Acetylamino-2,3-dihydrobenzofuranYield 52%

Procedure

NH2OH.HCl (7.3 g, 105 mmol) was added to a stirred solution of ketone 191 (14.2 g, 87.7 mmol) and pyridine (9.2 mL, 114 mmol) in MeOH (100 mL) and the mixture stirred at 20° C. for 16 h. The solvent was evaporated and the residue partitioned between brine and EtOAc. The organic fraction was dried and the solvent evaporated to give crude 1-(2,3-dihydro-1-benzofuran-5-yl)ethanone oxime (15.3 g, 99%). HCl gas was bubbled through a solution of the oxime (15.3 g, 86.5 mmol) in Ac2O (16.3 mL, 173 mmol) and HOAc (54 mL, 865 mmol), and the solution stood at 20° C. for 24 h. The precipitate was poured into ice/water, stirred for 2 h, the solid filtered and washed with water and dried. The aqueous fraction was extracted with DCM (2×50 mL), the combined organic extract dried and the solvent evaporated. The slurry was treated with water (20 mL) and evaporated several times to remove Ac2O. The combined solids were purified by chromatography, eluting with a gradient (50-100%) of EtOAc/pet. ether, to give acetamide 192 (7.94 g, 52%) as a white solid: mp 92-93° C. [lit. (Blade-Font, A.; de Mas Rocabayera, T. J. Chem. Soc. P1, 1982, 814848) mp 93° C.]; 1H NMR δ 7.47 (br s, 1H, H-4), 7.21 (br s, 1H, NH), 6.99 (dd, J=8.5, 2.1 Hz, 1H, H-6), 6.69 (d, J=8.5 Hz, 1H, H-7), 4.55 (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. filtrationthe solid filtered
  2. washwashed with water
  3. customdried
  4. extractionThe aqueous fraction was extracted with DCM (2×50 mL)
  5. extractionthe combined organic extract
  6. customdried
  7. customthe solvent evaporated
  8. additionThe slurry was treated with water (20 mL)
  9. customevaporated several times
  10. customto remove Ac2O
  11. customThe combined solids were purified by chromatography
  12. washeluting with a gradient (50-100%) of EtOAc/pet. ether

Sources & evidence

ORD record
ord-00df0ae308584c068d7f5000e3de585a
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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