1,2-Dimethoxyethane → HCID 15491032, compound

HRID 1954913Notes

Reaction equation

HRID 1954913 reaction equation
BrC1C(Br)[C:9]2[C:4](=[CH:5][C:6]([F:12])=[CH:7][CH:8]=2)/[C:3]/1=[CH:13]/[C:14]([NH2:16])=[O:15].[CH2:17]([CH2:20][O:21]C)[O:18]C>O.C(=O)([O-])[O-].[Ag+2]>[OH:21][CH:20]1[CH:17]([OH:18])[C:9]2[C:4](=[CH:5][C:6]([F:12])=[CH:7][CH:8]=2)/[C:3]/1=[CH:13]/[C:14]([NH2:16])=[O:15]

Participants

5

Reactant 2

HCID 80711,2-DimethoxyethaneHCID 69887281HCID 69887281, compound

Product 1

HCID 15491032HCID 15491032, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 178418647HCID 178418647, compoundCatalystHCID 962WaterSolvent2×

Procedure

A mixture of (Z)-2-(2,3-dibromo-6-fluoro-1-indanylidene)acetamide (0.54 g, 1.55 mmoles) and silver carbonate (0.56 g, 2.03 mmoles, Aldrich) in dimethoxyethane (15 mL) and water (30 mL) was refluxed for 6 hours. The mixture was stirred overnight at ambient temperature and refluxed again for 6 hours. The mixture was diluted with water (100 mL) and extracted with ethyl acetate (6×30 mL). The combined extracts were washed with water (100 mL) and brine (100 mL), and evaporated in vacuo. The residue was chromatographed on silica gel, eluting with hexane:ethyl acetate (2:1). The fractions containing the compound with Rf=0.15, eluting with ethyl acetate, were combined and evaporated in vacuo to give 0.12 g (35%) of crude (Z)-2-(2,3-dihydroxy-6-fluoro-1-indanylidene) acetamide as a beige solid. Recrystallization from ethyl acetate:hexane mixtures gave 0.037 g (11%) of (Z)-2-(2,3-dihydroxy-6-fluoro-1-indanylidene)acetamide as an off-white solid which was shown by 1H-NMR to be a mixture (85:15) of diastereomers, mp 212-220° C., 1H-NMR (DMSO-d6): d 7.82 (d, 2H, 7.28-7.76 (m, 3H), 6.96 (s, 1H), 6.80 (s, 0.15H), 6.54 (s, 0.85H), 6.51 and 6.12 (m, 0.3H), 5.92 (d, 1H), 4.81 (m, 1.7H); steady-state nOe: irradiation at 6.47d, observed 20% nOe at 7.38d.

Workup

  1. temperaturewas refluxed for 6 hours
  2. temperaturerefluxed again for 6 hours
  3. extractionextracted with ethyl acetate (6×30 mL)
  4. washThe combined extracts were washed with water (100 mL) and brine (100 mL)
  5. customevaporated in vacuo
  6. customThe residue was chromatographed on silica gel
  7. washeluting with hexane:ethyl acetate (2:1)
  8. additionThe fractions containing the compound with Rf=0.15
  9. washeluting with ethyl acetate
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-016e71858dfd417eb14233be09aa2990
Source dataset
uspto-grants-2000_09
Patent number
US06124284

Reaction notes

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