Hydrochloric Acid → 7-Hydroxy-3-(4-hydroxyphenyl)-3-methyl-4-(2-propenyl)chroman

HRID 398081Notes

Reaction equation

HRID 398081 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=O)[C:7]([C:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=3)([CH3:12])[CH2:8][O:9]2)=[CH:4][CH:3]=1.[H-].[CH2:22]([Al+]CC(C)C)[CH:23](C)[CH3:24].C1(C)C=CC=CC=1.[Cl-].[NH4+].Cl.C([Si](C)(C)C)C=C>O1CCCC1.ClCCCl.[I-].[Zn+2].[I-].CO>[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]([CH2:24][CH:23]=[CH2:22])[C:7]([C:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=3)([CH3:12])[CH2:8][O:9]2)=[CH:4][CH:3]=1

Participants

11

Reactant 6

HCID 313Hydrochloric Acid2×HCID 1140TolueneHCID 25517Ammonium Chloride2×HCID 69808AllyltrimethylsilaneHCID 21225700DiisobutylaluminumhydrideHCID 22033150HCID 22033150, compound

Product 1

HCID 230016937-Hydroxy-3-(4-hydroxyphenyl)-3-methyl-4-(2-propenyl)chromanYield 44%

Reagents, catalysts & solvents 4

HCID 9883512zinc(II)iodideCatalystHCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of (+)-7-hydroxy-3-(4-hydroxyphenyl)-3-methylchroman-4-one (2.0 g, 7.40 mmol) in anhydrous tetrahydrofuran (30 ml) was cooled to −78° C. To this solution, a solution of diisobutylaluminum hydride in toluene (1N, 22.94 ml, 22.94 mmol) was slowly added dropwise, and the resulting mixture was stirred for 35 minutes at −78° C. Methanol (1 ml) was added to the reaction mixture at −78° C., which was then warmed to 0° C. and further saturated aqueous ammonium chloride (5 ml) and concentrated hydrochloric acid (7 ml) were added to the mixture followed by stirring for 30 minutes. The reaction mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. After distilling off the solvent, zinc iodide (2.55 g, 7.98 mmol) was added to a suspension of the residue and allyltrimethylsilane (5.3 ml, 33.2 mmol) in 1,2-dichloroethane (80 ml) followed by stirring for 12 hours at room temperature. Saturated aqueous ammonium chloride (15 ml), methanol (10 ml) and concentrated hydrochloric acid (10 ml) were added to the reaction mixture, followed by stirring for 30 minutes. The reaction mixture was extracted twice with dichloromethane. The combined organic layers were washed with water and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/4) to give optically active 7-hydroxy-3-(4-hydroxyphenyl)-3-methyl-4-(2-propenyl)chroman (cis-configuration, 859 mg, Yield 44%).

Workup

  1. temperaturewhich was then warmed to 0° C.
  2. stirringby stirring for 30 minutes
  3. extractionThe reaction mixture was extracted twice with ethyl acetate
  4. washThe combined organic layers were washed with water and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. stirringby stirring for 12 hours at room temperature
  7. stirringby stirring for 30 minutes
  8. extractionThe reaction mixture was extracted twice with dichloromethane
  9. washThe combined organic layers were washed with water and saturated aqueous sodium chloride
  10. dry with materialdried over anhydrous magnesium sulfate
  11. distillationAfter distilling off the solvent
  12. customthe residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/4)

Sources & evidence

ORD record
ord-a6834dd2b6db4fcb99fe0b786b9c3cd6
Source dataset
uspto-grants-2003_08
Patent number
US06610733B2

Reaction notes

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