1,2-Dimethoxyethane → (Z)-2-(6-fluoro-2-hydroxy-1-indanylidene)acetamide

HRID 862768Notes

Reaction equation

HRID 862768 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(COC)[O:17]C>O.[N+]([O-])([O-])=O.[Ag+]>[F:11][C:6]1[CH:5]=[C:4]2[C:9]([CH2:10][CH:2]([OH:17])/[C:3]/2=[CH:12]\[C:13]([NH2:15])=[O:14])=[CH:8][CH:7]=1

Participants

5

Reactant 2

HCID 80711,2-DimethoxyethaneHCID 69887285(Z)-2-(2-bromo-6-fluoro-1-indanylidene)acetamide

Product 1

HCID 15491031(Z)-2-(6-fluoro-2-hydroxy-1-indanylidene)acetamideYield 28%

Reagents, catalysts & solvents 2

HCID 24470Silver NitrateCatalystHCID 962WaterSolvent

Procedure

A mixture of (Z)-2-(2-bromo-6-fluoro-1-indanylidene)acetamide (5.30 g, 19.25 mmoles) and silver nitrate (10.40 g, 61.18 mmoles, Aldrich) in dimethoxyethane (265 mL) and water (100 mL) was refluxed for 18 hours. The mixture was filtered, and the filtrate was diluted with water (700 mL) and extracted with ethyl acetate (6×100 mL). The combined extracts were washed with water (200 mL) and brine (200 mL), dried over magnesium sulfate, filtered, and evaporated in vacuo. The residue was chromatographed on silica gel, eluting with hexane:ethyl acetate (2:1), gradually increasing the polarity to hexane:ethyl acetate (1:1). The fractions containing the compound with Rf=0.18 were combined and evaporated in vacuo to give 1.13 g (28%) of crude (Z)-2-(6-fluoro-2-hydroxy-1-indanylidene)acetamide as an orange solid. Recrystallization from ethyl acetate:hexane mixtures gave 0.49 g (12%) of (Z)-2-(6-fluoro-2-hydroxy-1-indanylidene)acetamide as an off-white solid, mp 201°-202° C.; 1H-NMR (DMSO-d6): d 7.73 (d, 2H), 7.19-7.39 (m, 3H), 6.53 (m, 1H), 6.47 (m, 1H), 5.23 (m, 1H), 3.33 (dd, 1H, J=9.6 Hz, 17.0 Hz), and 2.81 (dd, 1H, J=1.6 Hz, 16.3 Hz); steady-state nOe: irradiation at 6.47 d, observed 20% nOe at 7.38 d.

Workup

  1. temperaturewas refluxed for 18 hours
  2. filtrationThe mixture was filtered
  3. additionthe filtrate was diluted with water (700 mL)
  4. extractionextracted with ethyl acetate (6×100 mL)
  5. washThe combined extracts were washed with water (200 mL) and brine (200 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was chromatographed on silica gel
  10. washeluting with hexane:ethyl acetate (2:1)
  11. temperaturegradually increasing the polarity to hexane:ethyl acetate (1:1)
  12. additionThe fractions containing the compound with Rf=0.18
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-07b922413ff94fdda8532997d485c2f1
Source dataset
uspto-grants-1998_02
Patent number
US05719186

Reaction notes

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