Iodine → N-(3-Hydroxy-3-(3-isopropylphenyl)-2,2,6,7-tetramethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide

HRID 2376569Notes

Reaction equation

HRID 2376569 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([CH3:10])[CH3:9].[Mg].II.[CH3:14][C:15]([CH3:35])([CH3:34])[CH2:16][C:17]([NH:19][C:20]1[C:21]([CH3:33])=[C:22]([CH3:32])[C:23]2[O:27][C:26]([CH3:29])([CH3:28])[C:25](=[O:30])[C:24]=2[CH:31]=1)=[O:18]>C1COCC1>[OH:30][C:25]1([C:7]2[CH:6]=[CH:5][CH:4]=[C:3]([CH:8]([CH3:10])[CH3:9])[CH:2]=2)[C:24]2[CH:31]=[C:20]([NH:19][C:17](=[O:18])[CH2:16][C:15]([CH3:35])([CH3:34])[CH3:14])[C:21]([CH3:33])=[C:22]([CH3:32])[C:23]=2[O:27][C:26]1([CH3:28])[CH3:29]

Participants

6

Reactant 4

HCID 807IodineHCID 23475o-BromocumeneHCID 5462224MagnesiumHCID 231138583,3-dimethyl-N-(2,2,6,7-tetramethyl-3-oxo-2,3-dihydro-1-benzofuran-5-yl)butanamide

Product 1

HCID 23114025N-(3-Hydroxy-3-(3-isopropylphenyl)-2,2,6,7-tetramethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamideYield 16.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1-bromo-2-isopropylbenzene (1.20 g, 6.03 mmol) in THF (5 mL) was added dropwise under an argon atmosphere to a mixture of magnesium (147 mg, 6.03 mmol) and a catalytic amount of iodine, and the mixture was stirred at 70° C. for 30 minutes. To the reaction solution was added dropwise a solution of 3,3-dimethyl-N-(2,2,6,7-tetramethyl-3-oxo-2,3-dihydro-1-benzofuran-5-yl)butanamide (350 mg, 1.15 mmol) obtained in Reference Example 65 in THF (3 mL), and the mixture was refluxed with heating for 12 hours. The reaction solution was added to ice and the product was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2) to obtain 79 mg (yield: 16%) of N-(3-hydroxy-3-(3-isopropylphenyl)-2,2,6,7-tetramethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide. To a solution of the compound (79 mg, 0.19 mmol) in trifluoroacetic acid (1 mL) was added with ice-cooling triethylsilane (44 mg, 0.38 mmol), and the mixture was stirred at room temperature for 1 hour. The reaction solution was added to water and the product was extracted with ethyl acetate. The organic layer was washed with an aqueous 1 N sodium hydroxide solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2) to obtain 39 mg (yield: 51%) of the title compound. Yield: 51%. Melting point: 188-189° C. (ethyl acetate-hexane).

Workup

  1. temperaturethe mixture was refluxed
  2. temperaturewith heating for 12 hours
  3. additionThe reaction solution was added to ice
  4. extractionthe product was extracted with ethyl acetate
  5. washThe organic layer was washed with water and saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2)

Sources & evidence

ORD record
ord-bf03b8e1f86f4bddb0156d0844f717a5
Source dataset
uspto-grants-2008_12
Patent number
US07465815B2

Reaction notes

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