2-(1,3-Dioxolan-2-yl)-3-bromo-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene → 2-(1,3-Dioxolan-2-yl)-3-(2,4-difluorobenzyl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene

HRID 1836893Notes

Reaction equation

HRID 1836893 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[C:15](Br)=[CH:14][C:13]2[C:12]([CH3:18])([CH3:17])[CH2:11][CH2:10][C:9]([CH3:20])([CH3:19])[C:8]=2[CH:7]=1.[Cl-].[F:22][C:23]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:24]=1[CH2:25][Zn+]>O1CCCC1>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[C:15]([CH2:25][C:24]2[CH:27]=[CH:28][C:29]([F:31])=[CH:30][C:23]=2[F:22])=[CH:14][C:13]2[C:12]([CH3:18])([CH3:17])[CH2:11][CH2:10][C:9]([CH3:20])([CH3:19])[C:8]=2[CH:7]=1

Participants

4

Reactant 2

HCID 234989352-(1,3-Dioxolan-2-yl)-3-bromo-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthaleneHCID 178505769HCID 178505769, compound

Product 1

HCID 234989192-(1,3-Dioxolan-2-yl)-3-(2,4-difluorobenzyl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthaleneYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2-(1,3-dioxolan-2-yl)-3-bromo-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene (250 mg, 0.74 mmol) and tetrakis(triphenylphospine)palladium(0) (21 mg, 0.018 mmol) under an argon atmosphere was added a 0.5 M tetrahydrofuran solution of 2,4-difluorobenzylzinc chloride (7.3 mL, 3.68 mmol). The reaction was stirred at reflux overnight and partitioned between saturated ammonium chloride solution and ethyl acetate. The organic layer was washed with brine, dried over MgSO4, and concentrated. The residue was purified by preparative thin layer chromatography on silica gel (5% ethyl acetate/hexane) to give 2-(1,3-dioxolan-2-yl)-3-(2,4-difluorobenzyl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene as a white crystalline solid (245 mg, 96%).

Workup

  1. temperatureat reflux overnight
  2. custompartitioned between saturated ammonium chloride solution and ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by preparative thin layer chromatography on silica gel (5% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-d286171b18094f5eaf77c3d661208194
Source dataset
uspto-grants-2004_08
Patent number
US06777418B2

Reaction notes

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