Ammonium Chloride → (3RS,4RS)-4-allyl-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman

HRID 1268080Notes

Reaction equation

HRID 1268080 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.[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-].[NH4+].[CH2:31]([Si](C)(C)C)[CH:32]=[CH2:33]>O1CCCC1.O.[I-].[Zn+2].[I-].C(OCC)(=O)C.CCCCCC>[CH2:33]([CH:7]1[C:6]2[C:11](=[CH:12][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[S:10][CH2:9][C:8]1([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[CH3:13])[CH:32]=[CH2:31]

Participants

9

Reactant 4

HCID 25517Ammonium ChlorideHCID 69808AllyltrimethylsilaneHCID 10979954HCID 10979954, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 22033345(3RS,4RS)-4-allyl-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochromanYield 60.3%

Reagents, catalysts & solvents 4

HCID 9883512zinc(II)iodideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
-78 °C

Procedure

7-Methoxy-3-(4-methoxyphenyl)-3-methylthiochroman-4-one(2.24 g, 6.823 mmol) prepared according to the known method in WO98/25916 was dissolved in dry tetrahydrofuran(30 ml) and then cooled to −78° C. Lithium aluminum hydride(1N solution in THF, 3.41 ml, 3.412 mmol) was added dropwise thereto and the resulting mixture was stirred overnight at room temperature. The reaction mixture was treated with saturated aqueous ammonium chloride solution(100 ml), extracted twice with ethyl acetate(100 ml), washed with water and saturated saline solution, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and the residue was dissolved in 1,2-dichloroethane(30 ml). Zinc iodide(2.61 g, 8.188 mmol) and allyltrimethylsilane(2.17 ml, 13.646 mmol) were added dropwise thereto under cooling to 0° C. and the resulting mixture was stirred overnight at room temperature. The reaction mixture was diluted with water(200 ml), extracted twice with dichloromethane(200 ml), washed with water and saturated saline solution, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and the residue thus obtained was purified by silica gel column chromatography(eluent:ethyl acetate/n-hexane=1/4, v/v) to give 1.4 g(Yield 58%) of the title compound.

Workup

  1. extractionextracted twice with ethyl acetate(100 ml)
  2. washwashed with water and saturated saline solution
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. dissolutionthe residue was dissolved in 1,2-dichloroethane(30 ml)
  7. temperatureunder cooling to 0° C.
  8. stirringthe resulting mixture was stirred overnight at room temperature
  9. extractionextracted twice with dichloromethane(200 ml)
  10. washwashed with water and saturated saline solution
  11. dry with materialdried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationThe filtrate was concentrated under reduced pressure
  14. customthe residue thus obtained
  15. customwas purified by silica gel column chromatography(eluent

Sources & evidence

ORD record
ord-d93885b9616f43f9a0be2a4248337d39
Source dataset
uspto-grants-2003_04
Patent number
US06555571B2

Reaction notes

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