Sodium hydride → (s)-2,2-dimethyl-4-((4-(2-(4-((R)-oxiran-2-ylmethoxy)phenyl)propan-2-yl)phenoxy)methyl)-1,3-dioxolane

HRID 705318Notes

Reaction equation

HRID 705318 reaction equation
[H-].[Na+].[CH3:3][C:4]1([CH3:27])[O:8][C@@H:7]([CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([C:20]3[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=3)([CH3:19])[CH3:18])=[CH:13][CH:12]=2)[CH2:6][O:5]1.CC1C=CC(S(O[CH2:39][C@@H:40]2[O:42][CH2:41]2)(=O)=O)=CC=1>CN(C)C=O>[CH3:3][C:4]1([CH3:27])[O:8][C@@H:7]([CH2:9][O:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]([C:20]3[CH:21]=[CH:22][C:23]([O:26][CH2:39][C@H:40]4[CH2:41][O:42]4)=[CH:24][CH:25]=3)([CH3:18])[CH3:19])=[CH:15][CH:16]=2)[CH2:6][O:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 154187Glycidyl tosylate, (R)-HCID 71257395(S)-4-(2-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)propan-2-yl)phenol

Product 1

HCID 89407171(s)-2,2-dimethyl-4-((4-(2-(4-((R)-oxiran-2-ylmethoxy)phenyl)propan-2-yl)phenoxy)methyl)-1,3-dioxolaneYield 97.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (60% dispersion in mineral oil, 391 mg, 9.78 mmol, 1.5 equiv) was added slowly to a stirred solution of (S)-4-(2-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)propan-2-yl)phenol (2230 mg, 6.52 mmol, 1 equiv) in anhydrous dimethyl formamide (15 mL), at room temperature, and the contents were stirred under an atmosphere of argon for 30 min. A solution of (2R)-(−)-glycidyl tosylate 98% (2230 mg, 9.78 mmol, 1.5 equiv) in anhydrous dimethyl formamide (5 mL) was added via syringe and the mixture was allowed to react at room temperature for 16 h. Then, the reaction was quenched by the addition of a saturated solution of ammonium chloride (10 mL), and the mixture was extracted with ethyl acetate (3×20 mL). The organic layer was washed with deionized water (20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel (eluent: 20% to 40% ethyl acetate in hexane) to provide the title compound (2.53 g, 94%) as a clear foam.

Workup

  1. customto react at room temperature for 16 h
  2. customThen, the reaction was quenched by the addition of a saturated solution of ammonium chloride (10 mL)
  3. extractionthe mixture was extracted with ethyl acetate (3×20 mL)
  4. washThe organic layer was washed with deionized water (20 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by flash column chromatography on silica gel (eluent: 20% to 40% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-f64903f705f4458eb440f78c7327ec4a
Source dataset
uspto-grants-2015_11
Patent number
US09173939B2

Reaction notes

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