Sodium Chloride → (3S,4S)-7-methoxy-3-(4-methoxyphenyl)-3-methyl-4-(2-propenyl)thiochroman

HRID 398075Notes

Reaction equation

HRID 398075 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7](=O)[C@:8]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)([CH3:13])[CH2:9][S:10]2)=[CH:5][CH:4]=1.[BH4-].[Na+].[Cl-].[Na+].[CH2:27]([Si](C)(C)C)[CH:28]=[CH2:29]>O1CCCC1.C(O)C.ClCCl.[I-].[Zn+2].[I-].O.CO>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C@@H:7]([CH2:29][CH:28]=[CH2:27])[C@:8]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)([CH3:13])[CH2:9][S:10]2)=[CH:5][CH:4]=1

Participants

11

Reactant 4

HCID 5234Sodium ChlorideHCID 69808AllyltrimethylsilaneHCID 4311764Sodium borohydrideHCID 12043768(3R)-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman-4-one

Product 1

HCID 12043773(3S,4S)-7-methoxy-3-(4-methoxyphenyl)-3-methyl-4-(2-propenyl)thiochromanYield 58.3%

Reagents, catalysts & solvents 6

HCID 9883512zinc(II)iodideCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

The (3R)-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman-4-one prepared in Example 1 (11.4 g, 36.26 mmol) was dissolved in tetrahydrofuran (40 ml) and ethanol (20 ml). To this solution, sodium borohydride (2.74 g, 72.51 mmol) was added at −78° C., and the resulting mixture was stirred for 15 hours at room temperature. After the reaction was completed, dichloromethane, methanol and saturated aqueous sodium chloride were added to the reaction mixture, which was then extracted under heating conditions. The organic layer was dried over anhydrous magnesium sulfate. After distilling off the solvent, allyltrimethylsilane (10.74 ml, 67.6 mmol) and zinc iodide (12.9 g, 40.57 mmol) were added to a solution of the residue in dichloromethane (300 ml) followed by stirring for 15 hours at room temperature. Water was added to the reaction mixture, which was then extracted with dichloromethane. The organic layer was washed with saturated aqueous ammonium chloride and dried over anhydrous magnesium sulfate, and the resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/90) to give (3S,4S)-7-methoxy-3-(4-methoxyphenyl)-3-methyl-4-(2-propenyl)thiochroman (7.2 g, Yield 58%) as an oil.

Workup

  1. extractionwas then extracted under heating conditions
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. stirringby stirring for 15 hours at room temperature
  4. extractionwas then extracted with dichloromethane
  5. washThe organic layer was washed with saturated aqueous ammonium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/90)

Sources & evidence

ORD record
ord-facc9632297d4ab782f470fd52227e34
Source dataset
uspto-grants-2003_08
Patent number
US06610733B2

Reaction notes

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