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

HRID 2376547Notes

Reaction equation

HRID 2376547 reaction equation
Cl[CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Mg].II.[CH3:13][C:14]([CH3:34])([CH3:33])[CH2:15][C:16]([NH:18][C:19]1[C:20]([CH3:32])=[C:21]([CH3:31])[C:22]2[O:26][C:25]([CH3:28])([CH3:27])[C:24](=[O:29])[C:23]=2[CH:30]=1)=[O:17]>C1COCC1>[OH:29][C:24]1([CH2:2][CH2:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:23]2[CH:30]=[C:19]([NH:18][C:16](=[O:17])[CH2:15][C:14]([CH3:34])([CH3:33])[CH3:13])[C:20]([CH3:32])=[C:21]([CH3:31])[C:22]=2[O:26][C:25]1([CH3:27])[CH3:28]

Participants

6

Reactant 4

HCID 807IodineHCID 2314961-Chloro-2-phenylethaneHCID 5462224MagnesiumHCID 231138583,3-dimethyl-N-(2,2,6,7-tetramethyl-3-oxo-2,3-dihydro-1-benzofuran-5-yl)butanamide

Product 1

HCID 23113920N-(3-Hydroxy-2,2,6,7-tetramethyl-3-(2-phenylethyl)-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamideYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-chloroethylbenzene (648 mg, 4.6 mmol) in THF (5 mL) was added dropwise under an argon atmosphere to a mixture of magnesium (112 mg, 4.6 mmol) and a catalytic amount of iodine, and the mixture was stirred 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 (300 mg, 0.98 mmol) obtained in Reference Example 65 in THF (3 mL), and the mixture was stirred at room temperature for 1 hour. The reaction solution was added to ice and the product was extracted with ethyl acetate. The extract 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=2:3) and recrystallized from ethyl acetate-hexane to obtain 201 mg (yield: 51%) of the title compound. Melting point: 99-100° C.

Workup

  1. additionThe reaction solution was added to ice
  2. extractionthe product was extracted with ethyl acetate
  3. washThe extract was washed with water and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=2:3)
  7. customrecrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-7335226e6b5741fc8ec542298c72d14a
Source dataset
uspto-grants-2008_12
Patent number
US07465815B2

Reaction notes

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