Water → Tert-butyl(7-(1-hydroxy-1-(4-isopropylphenyl)ethyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-yl)carbamate

HRID 2376542Notes

Reaction equation

HRID 2376542 reaction equation
Br[C:2]1[C:10]2[O:9][CH2:8][CH2:7][C:6]=2[C:5]([CH3:11])=[C:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C:3]=1[CH3:20].C([Li])CCC.[CH3:26][CH:27]([C:29]1[CH:34]=[CH:33][C:32]([C:35]([CH3:37])=[O:36])=[CH:31][CH:30]=1)[CH3:28].O>C1COCC1>[OH:36][C:35]([C:2]1[C:10]2[O:9][CH2:8][CH2:7][C:6]=2[C:5]([CH3:11])=[C:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C:3]=1[CH3:20])([C:32]1[CH:33]=[CH:34][C:29]([CH:27]([CH3:28])[CH3:26])=[CH:30][CH:31]=1)[CH3:37]

Participants

6

Reactant 4

HCID 962WaterHCID 125784-IsopropylacetophenoneHCID 86612363tert-Butyl (7-bromo-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-yl)carbamateHCID 178418339Butyllithium

Product 1

HCID 86612348Tert-butyl(7-(1-hydroxy-1-(4-isopropylphenyl)ethyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-yl)carbamateYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixed solution of tert-butyl (7-bromo-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-yl)carbamate obtained in Example 222 (500 mg, 1.46 mmol) and cerous chloride (360 mg, 3.21 mmol) in THF (8 mL) was added dropwise at −78° C. under an argon atmosphere n-butyllithium (1.6 M hexane solution, 2.0 mL, 3.21 mmol). The mixture was stirred at the same temperature for 30 minutes, and then to the reaction solution was added dropwise a solution of 4-isopropylacetophenone (261 mg, 1.61 mmol) in THF (4 mL) and the resulting mixture was stirred for 30 minutes and elevated to room temperature. Water was added to the reaction solution and the product was extracted with ethyl acetate. The combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=2:3) to obtain 118 mg (yield: 19%) the title compound. Melting point: 185-186° C. (ethyl acetate-hexane).

Workup

  1. stirringthe resulting mixture was stirred for 30 minutes
  2. customelevated to room temperature
  3. extractionthe product was extracted with ethyl acetate
  4. washThe combined organic layers were washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=2:3)

Sources & evidence

ORD record
ord-9016a25cbbe2466d8924eda44e77fad5
Source dataset
uspto-grants-2008_12
Patent number
US07465815B2

Reaction notes

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