Iodine → HCID 67403681, compound

HRID 575970Notes

Reaction equation

HRID 575970 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[CH:3]=1.[Mg].II.[C:13]([N:20]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21]1)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].[Cl-].[NH4+]>O1CCCC1>[F:9][C:4]1[CH:3]=[C:2]([C:22]2([OH:25])[CH2:23][CH2:24][N:20]([C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])[CH2:21]2)[CH:7]=[C:6]([F:8])[CH:5]=1

Participants

7

Reactant 5

HCID 807IodineHCID 25517Ammonium ChlorideHCID 1363131-Bromo-3,5-difluorobenzeneHCID 471360Tert-butyl 3-oxopyrrolidine-1-carboxylateHCID 5462224Magnesium

Product 1

HCID 67403681HCID 67403681, compoundYield 30.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-bromo-3,5-difluorobenzene (8 g, 41.4 mmol) in dry tetrahydrofuran (100 ml), under nitrogen, was added magnesium turnings (0.99 g, 41.4 mmol) and one crystal of iodine. The mixture was refluxed for 1 h, cooled to ambient temperature and a solution of 1-N-boc-3-pyrrolidone (7.66 g, 41.4 mmol) in dry tetrahydrofuran (40 ml) was added drop wise. The resulting mixture was refluxed 1 h, cooled to ambient temperature, aqueous saturated ammonium chloride solution (50 ml) was added and the mixture was extracted with ethylacetate (3×50 ml). The combined organic phase was washed with brine, dried (Na2SO4), filtered and evaporated to dryness. The crude product was purified by flash column chromatography (ethylacetate/isooctane, 1:9 to 1:1) to give the title compound (3.8 g, 30%). MS m/z (rel. intensity, 70 eV) 299 (M+, 1), 243 (30), 198 (39), 127 (36), 57 (bp).

Workup

  1. temperatureThe mixture was refluxed for 1 h
  2. temperatureThe resulting mixture was refluxed 1 h
  3. temperaturecooled to ambient temperature
  4. extractionthe mixture was extracted with ethylacetate (3×50 ml)
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customThe crude product was purified by flash column chromatography (ethylacetate/isooctane, 1:9 to 1:1)

Sources & evidence

ORD record
ord-563bb46668884287b88dc248707fbe59
Source dataset
uspto-grants-2015_05
Patent number
US09035073B2

Reaction notes

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