Hydrochloric Acid → HCID 18546252, compound

HRID 1267756Notes

Reaction equation

HRID 1267756 reaction equation
[CH2:1]([C:3]1(C2C=CC(OC)=CC=2)[C:12](=O)[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[CH:9][CH:10]=2)[S:5][CH2:4]1)[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl.[CH2:31]([Si](C)(C)C)[CH:32]=[CH2:33]>O1CCCC1.[I-].[Zn+2].[I-].O.CO.C(OCC)(=O)C>[CH2:32]([C:31]1([C:11]2[CH:10]=[CH:9][C:8]([O:14][CH3:15])=[CH:7][CH:6]=2)[CH:12]([CH2:3][CH:1]=[CH2:2])[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[CH:9][CH:10]=2)[S:5][CH2:4]1)[CH3:33]

Participants

10

Reactant 4

HCID 313Hydrochloric Acid2×HCID 69808AllyltrimethylsilaneHCID 18546279HCID 18546279, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 18546252HCID 18546252, compoundYield 117.8%

Reagents, catalysts & solvents 5

HCID 9883512zinc(II)iodideCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of 3-ethyl-7-methoxy-3-(4-methoxyphenyl)-thiochroman-4-one (13.7 g, 41.8 mmol) in anhydrous tetrahydrofuran (100 ml) was added dropwise to a solution of lithium aluminum hydride (950 mg, 25 mmol) in anhydrous tetrahydrofuran (100 ml) at −78° C. under argon atmosphere, and the resulting mixture was warmed to −20° C. over 1 hour. Ethyl acetate, methanol and 2N aqueous hydrochloric acid were added sequentially to the reaction mixture, which was then filtered through cellite. After extraction with ethyl acetate, the organic layer was washed with saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. After distilling off the solvent, the resulting residue (13.10 g) was dissolved in 1,2-dichloroethane (360 ml) and then mixed with allyltrimethylsilane (12.47 ml, 78.75 mmol). Zinc iodide (15.08 g, 47.27 mmol) was added to this solution at 0° C. under argon atmosphere, and the resulting mixture was stirred for 4 hours at 40° C. Water and dilute hydrochloric acid were added sequentially to this mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, 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 flash column chromatography (eluent: hexane/ethyl acetate=20/1) to give (3RS,4RS)-3-ethyl-7-methoxy-3-(4-methoxyphenyl)-4-(2-propenyl)thiochroman (8.73 g, Yield 62% for 2 steps).

Workup

  1. filtrationwas then filtered through cellite
  2. extractionAfter extraction with ethyl acetate
  3. washthe organic layer was washed with saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationAfter distilling off the solvent
  6. dissolutionthe resulting residue (13.10 g) was dissolved in 1,2-dichloroethane (360 ml)
  7. extractionwas then extracted with ethyl acetate
  8. washThe organic layer was washed with saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride
  9. dry with materialdried over anhydrous magnesium sulfate
  10. distillationAfter distilling off the solvent
  11. customthe residue was purified by silica gel flash column chromatography (eluent: hexane/ethyl acetate=20/1)

Sources & evidence

ORD record
ord-e458802ce5c14d0a9bd583fe370192ad
Source dataset
uspto-grants-2003_04
Patent number
US06552068B1

Reaction notes

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