Formaldehyde → 6-Bromo-5-fluoro-2-methylene-2,3-dihydro-1H-inden-1-one

HRID 1468080Notes

Reaction equation

HRID 1468080 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][C:8]2=[O:11])=[CH:4][C:3]=1[F:12].C=O.F[C:16](F)(F)C([O-])=O.C[NH2+]C1C=CC=CC=1>C1COCC1>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[CH2:16])[C:8]2=[O:11])=[CH:4][C:3]=1[F:12]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 2724109N-Methylanilinium trifluoroacetateHCID 198011566-Bromo-5-fluoro-2,3-dihydro-1H-inden-1-one

Product 1

HCID 867066926-Bromo-5-fluoro-2-methylene-2,3-dihydro-1H-inden-1-oneYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

6-Bromo-5-fluoro-2,3-dihydro-1H-inden-1-one (commercially available), 4 g, 17.5 mmol), paraformaldehyde (2.48 g, 78.6 mmol) and N-methylanilinium trifluoroacetate (5.79 g, 26.2 mmol) were dissolved in anhydrous THF (80 mL) and refluxed overnight. The mixture was cooled to r.t. and concentrated. The residue was re-dissolved in EtOAc and brine. The phases were separated and the organic phase was dried over sodium sulfate and concentrated. The product was purified by flash column chromatography using heptane/EtOAc 7:1 as eluent affording the title compound (2.99 g, 71% yield). 1H NMR (400 MHz, CDCl3) δ ppm 3.73 (s, 3 H) 5.69 (m, 1 H) 6.39 (m, 1 H) 7.25 (s, 2 H) 8.10 (d, 1 H); MS (EI) m/z 240, 242 M+.

Workup

  1. temperaturerefluxed overnight
  2. concentrationconcentrated
  3. dissolutionThe residue was re-dissolved in EtOAc
  4. customThe phases were separated
  5. dry with materialthe organic phase was dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe product was purified by flash column chromatography

Sources & evidence

ORD record
ord-57c38aa1a07946b3959790b4caa4d9fd
Source dataset
uspto-grants-2015_04
Patent number
US09000183B2

Reaction notes

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