Iodine → HCID 23114307, compound

HRID 2376544Notes

Reaction equation

HRID 2376544 reaction equation
[Mg].II.[CH:4]([C:7]1[CH:12]=[CH:11][C:10](Br)=[CH:9][CH:8]=1)([CH3:6])[CH3:5].[CH:14]([C:16]1[C:24]2[O:23][CH2:22][CH:21]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:20]=2[C:19]([CH3:31])=[C:18]([NH:32][C:33](=[O:39])[CH2:34][C:35]([CH3:38])([CH3:37])[CH3:36])[C:17]=1[CH3:40])=[O:15]>C1COCC1>[OH:15][CH:14]([C:10]1[CH:11]=[CH:12][C:7]([CH:4]([CH3:6])[CH3:5])=[CH:8][CH:9]=1)[C:16]1[C:24]2[O:23][CH2:22][CH:21]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:20]=2[C:19]([CH3:31])=[C:18]([NH:32][C:33](=[O:39])[CH2:34][C:35]([CH3:36])([CH3:37])[CH3:38])[C:17]=1[CH3:40]

Participants

6

Reactant 4

HCID 807IodineHCID 114621-Bromo-4-isopropylbenzeneHCID 5462224MagnesiumHCID 23113994HCID 23113994, compound

Product 1

HCID 23114307HCID 23114307, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of magnesium (119 mg, 4.91 mmol) and a catalytic amount of iodine was added dropwise under an argon atmosphere a solution of 4-isopropyl-1-bromobenzene (978 mg, 4.91 mmol) in THF (10 mL) and the mixture was stirred at room temperature for 20 minutes. To the reaction solution was added dropwise a solution of N-(7-formyl-4,6-dimethyl-3-phenyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide (200 mg, 0.547 mmol) obtained in Example 232 in THF (5 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 organic layer was washed with 1 N hydrochloric acid and water, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2) to obtain N-(7-(hydroxy(4-isopropylphenyl)methyl)-4,6-dimethyl-3-phenyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide. To a mixture of the compound and trifluoroacetic acid (5 mL) was added with ice-cooling triethylsilane (0.161 mL, 1.01 mmol), and the mixture was stirred at room temperature for 30 minutes. After the reaction solution was concentrated under reduced pressure, to the residue was added an aqueous saturated sodium bicarbonate solution and the aqueous layer was made alkaline, and the mixture 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 (hexane:ethyl acetate=4:1) and crystallized from hexane to obtain 70 mg (yield: 28%) of the title compound. Melting point: 137-141° C. (ethyl acetate-hexane).

Workup

  1. stirringthe mixture was stirred at room temperature for 1 hour
  2. additionThe reaction solution was added to ice
  3. extractionthe product was extracted with ethyl acetate
  4. washThe organic layer was washed with 1 N hydrochloric acid and water
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2)

Sources & evidence

ORD record
ord-9b8e3c83b4d84f2b8391e8c221ae0ece
Source dataset
uspto-grants-2008_12
Patent number
US07465815B2

Reaction notes

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