1,1-Dibromoethane → 4-(4-t-Butyldimethylsilyloxyphenyl)-4-hydroxy-7-methoxymethyloxy-3-[4-(methoxymethyloxy)phenyl]-3-methylthiochroman

HRID 1859340Notes

Reaction equation

HRID 1859340 reaction equation
BrC(Br)C.[Mg].Br[C:7]1[CH:12]=[CH:11][C:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])=[CH:9][CH:8]=1.[CH3:21][O:22][CH2:23][O:24][C:25]1[CH:34]=[C:33]2[C:28]([C:29](=[O:46])[C:30]([C:36]3[CH:41]=[CH:40][C:39]([O:42][CH2:43][O:44][CH3:45])=[CH:38][CH:37]=3)([CH3:35])[CH2:31][S:32]2)=[CH:27][CH:26]=1.[Cl-].[NH4+]>O1CCCC1>[Si:14]([O:13][C:10]1[CH:11]=[CH:12][C:7]([C:29]2([OH:46])[C:28]3[C:33](=[CH:34][C:25]([O:24][CH2:23][O:22][CH3:21])=[CH:26][CH:27]=3)[S:32][CH2:31][C:30]2([C:36]2[CH:37]=[CH:38][C:39]([O:42][CH2:43][O:44][CH3:45])=[CH:40][CH:41]=2)[CH3:35])=[CH:8][CH:9]=1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

7

Reactant 5

HCID 112011,1-DibromoethaneHCID 25517Ammonium ChlorideHCID 4227167(4-Bromophenoxy)(tert-butyl)dimethylsilaneHCID 5462224MagnesiumHCID 220332467-Methoxymethoxy-3-(4-methoxymethoxyphenyl)-3-methylthiochroman-4-one

Product 1

HCID 221236264-(4-t-Butyldimethylsilyloxyphenyl)-4-hydroxy-7-methoxymethyloxy-3-[4-(methoxymethyloxy)phenyl]-3-methylthiochromanYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
60 °C

Procedure

Under argon atmosphere dibromoethane (0.11 ml, 1.28 mmol) was added dropwise to tetrahydrofuran suspension (5 ml) of magnesium turning (224 mg, 9.33 mmol) and the mixture was stirred for 10 minutes at 60° C. At the same temperature, tetrahydrofuran solution (5 ml) of p-bromo-t-butyldimethylsilyloxybenzene (2.30 g, 8.01 mmol) was added dropwise thereto and the mixture was heated under refluxing for 1.5 hours. To the resulting solution was added dropwise tetrahydrofuran solution (5 ml) of 7-methoxymethyloxy-3-[4-(methoxymethyloxy)phenyl]-3-methylthiochroman-4-one (1.00 g, 2.67 mmol) and the mixture was heated under refluxing for 3 hours. After adding saturated aqueous ammonium chloride solution, the reaction solution was extracted with ethyl acetate, and the organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and then distilled under reduced pressure to remove the solvent. The crude product thus obtained was purified with silica gel column chromatography (ethyl acetate:hexane=1:4) to obtain 1.29 g (yield: 83%) of the title compound.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder refluxing for 1.5 hours
  3. temperaturethe mixture was heated
  4. temperatureunder refluxing for 3 hours
  5. extractionthe reaction solution was extracted with ethyl acetate
  6. washthe organic layer was washed with saturated saline
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationdistilled under reduced pressure
  9. customto remove the solvent
  10. customThe crude product thus obtained
  11. customwas purified with silica gel column chromatography (ethyl acetate:hexane=1:4)

Sources & evidence

ORD record
ord-591c0d9dd95c4acda0e8e235b6a23959
Source dataset
uspto-grants-2000_11
Patent number
US06153768

Reaction notes

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