Methanol → (Z)-2-(6-fluoro-2-methoxy-1-indanylidene)acetamide

HRID 862769Notes

Reaction equation

HRID 862769 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].[CH3:16][OH:17]>[N+]([O-])([O-])=O.[Ag+]>[F:11][C:6]1[CH:5]=[C:4]2[C:9]([CH2:10][CH:2]([O:17][CH3:16])/[C:3]/2=[CH:12]\[C:13]([NH2:15])=[O:14])=[CH:8][CH:7]=1

Participants

4

Reactant 2

HCID 887MethanolHCID 69887285(Z)-2-(2-bromo-6-fluoro-1-indanylidene)acetamide

Product 1

HCID 9837389(Z)-2-(6-fluoro-2-methoxy-1-indanylidene)acetamideYield 32%

Reagents, catalysts & solvents 1

HCID 24470Silver NitrateCatalyst2×

Procedure

A mixture of (Z)-2-(2-bromo-6-fluoro-1-indanylidene)acetamide (2.60 g, 9.60 mmoles) and silver nitrate (5.10 g, 27.43 mmoles, Aldrich) in methanol (200 mL) was refluxed for 8 hours. Additional silver nitrate (5.10 g, 27.43 mmoles) was added and the mixture was refluxed for 18 hours. The mixture was filtered, and the filtrate was evaporated in vacuo. The residue was chromatographed on silica gel, eluting with hexane:ethyl acetate (1:4), gradually increasing the polarity to 100% ethyl acetate. The fractions containing the compound with Rf=0.15 with hexane:ethyl acetate (1:1) as the eluant were combined and evaporated in vacuo and dried in a vacuum at 50° C. for 18 hours to give 0.68 g (32%) of crude (Z)-2-(6-fluoro-2-methoxy-1-indanylidene)acetamide as a tan solid. Recrystallization from ethyl acetate:hexane mixtures gave 0.49 g (23%) of (Z)-2-(6-fluoro-2-methoxy-1-indanylidene)acetamide as an off-white solid, mp 128°-130° C.; 1H-NMR (DMSO-d6): d 7.13-7.48 (m, 5H), 6.54 (s, 1H), 5.34 (d, 1H), 3.25 (s, 3H), 3.05 (dd, 1H, J=5.7 Hz, 17.3 Hz), and 2.87 (d, 1H, J=17.1 Hz).

Workup

  1. temperaturewas refluxed for 8 hours
  2. temperaturethe mixture was refluxed for 18 hours
  3. filtrationThe mixture was filtered
  4. customthe filtrate was evaporated in vacuo
  5. customThe residue was chromatographed on silica gel
  6. washeluting with hexane:ethyl acetate (1:4)
  7. temperaturegradually increasing the polarity to 100% ethyl acetate
  8. additionThe fractions containing the compound with Rf=0.15 with hexane:ethyl acetate (1:1) as the eluant
  9. customevaporated in vacuo
  10. customdried in a vacuum at 50° C. for 18 hours

Sources & evidence

ORD record
ord-61ffe07b5d9b4072867eabc83fce7bf3
Source dataset
uspto-grants-1998_02
Patent number
US05719186

Reaction notes

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