Acetic Acid → (Z)-2-(2-acetoxy-6-fluoro-1-indanylidene)acetamide

HRID 862770Notes

Reaction equation

HRID 862770 reaction equation
Br[CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][C:6]([F:11])=[CH:7][CH:8]=2)/[C:3]/1=[CH:12]/[C:13]([NH2:15])=[O:14].[C:16]([O-:19])(=[O:18])[CH3:17].[K+].C1OCCOCCOCCOCCOCCOC1.C(O)(=O)C>C(#N)C.C(O)C>[C:16]([O:19][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][C:6]([F:11])=[CH:7][CH:8]=2)/[C:3]/1=[CH:12]/[C:13]([NH2:15])=[O:14])(=[O:18])[CH3:17]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 2855718-Crown-6HCID 517044Potassium AcetateHCID 69887285(Z)-2-(2-bromo-6-fluoro-1-indanylidene)acetamide

Product 1

HCID 19698781(Z)-2-(2-acetoxy-6-fluoro-1-indanylidene)acetamideYield 46.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of (Z)-2-(2-bromo-6-fluoro-1-indanylidene)acetamide (0.51 g, 1.90 mmoles), potassium acetate (0.37 g, 3.80 mmoles), and 18-crown-6 (0.06 g, 0.24 mmoles, Aldrich) in acetonitrile (20 mL) and ethanol (10 mL) was sonicated using a Sonicor ultrasonicator for 2 hours, allowing the temperature to rise to 35° C. The mixture was stirred overnight at ambient temperature. Glacial acetic acid (3 mL) was added and the mixture was sonicated for 1.5 hours allowing the temperature to rise to 50° C. The mixture was stirred overnight at ambient temperature and evaporated in vacuo. The residue was dissolved in dichloromethane (100 mL), washed with water (2×50 mL) and evaporated in vacuo. The residue was chromatographed on silica gel eluting with hexane:ethyl acetate (3:1) gradually increasing the polarity to 100% ethyl acetate. The fractions containing the compound with Rf=0.3 in hexane:ethyl acetate (1:1) were combined and evaporated in vacuo to give a solid which was washed with hexane and dried in a vacuum at 50° C. for 18 hours to give 0.22 g (46%) of (Z)-2-(2-acetoxy-6-fluoro-1-indanylidene)acetamide as a white solid, mp 202°-203° C.; 1H-NMR (DMSO-d6): d 7.49 and 7.08 (d, 2H), 7.19-7.38 (m, 3H), 6.57 (s, 1H), 6.42 (d, 1H), 3.39 (dd, 1H, J=6.9 Hz, 17.7 Hz), and 2.82 (d, 1H, J=18.0 Hz), 1.91 (s, 3H); steady-state nOe: irradiation at 6.57 d, observed 22% nOe at 7.35 d.

Workup

  1. customwas sonicated
  2. customfor 2 hours
  3. customto rise to 35° C
  4. customthe mixture was sonicated for 1.5 hours
  5. customto rise to 50° C
  6. stirringThe mixture was stirred overnight at ambient temperature
  7. customevaporated in vacuo
  8. dissolutionThe residue was dissolved in dichloromethane (100 mL)
  9. washwashed with water (2×50 mL)
  10. customevaporated in vacuo
  11. customThe residue was chromatographed on silica gel eluting with hexane:ethyl acetate (3:1)
  12. temperaturegradually increasing the polarity to 100% ethyl acetate
  13. additionThe fractions containing the compound with Rf=0.3 in hexane:ethyl acetate (1:1)
  14. customevaporated in vacuo
  15. customto give a solid which
  16. washwas washed with hexane
  17. customdried in a vacuum at 50° C. for 18 hours

Sources & evidence

ORD record
ord-62fa472958114a0d85e9ebba65e99c0e
Source dataset
uspto-grants-1998_02
Patent number
US05719186

Reaction notes

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