Ethyl Acetate → [7-(Benzyloxy)-8-(2-hydroxyethyl)-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate

HRID 49251Notes

Reaction equation

HRID 49251 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][C@@H:13]2[O:18][C:17]3[C:19]([CH2:31][CH:32]=C)=[C:20]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.I([O-])(=O)(=O)=[O:35].[Na+].C(OCC)(=O)C.[BH4-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.O.[Os](=O)(=O)(=O)=O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]2[O:18][C:17]3[C:19]([CH2:31][CH2:32][OH:35])=[C:20]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 169536Tetrabutylammonium borohydrideHCID 23667635Sodium periodateHCID 88025780[(2R)-8-allyl-7-(benzyloxy)-2,3-dihydro-1,4-bezodioxin-2-yl]methyl 4-methylbenzenesulfonate

Product 1

HCID 18546019[7-(Benzyloxy)-8-(2-hydroxyethyl)-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3.9 g (8.4 mmole) of [(2R)-8-allyl-7-(benzyloxy)-2,3-dihydro-1,4-bezodioxin-2-yl]methyl 4-methylbenzenesulfonate in 300 mL of tetrahydrofuran was added 1.8 mL (0.30 mmole) of 4% aqueous osmium tetroxide. The solution was stirred at room temperature under nitrogen for 30 minutes, then a solution of 9.0 g (40 mmole) of sodium periodate in 75 mL of water was added dropwise over a 30 10 minute period. The mixture was allowed to stir at room temperature under nitrogen for 15 hours. Ethyl acetate (400 mL) was then added and the solution was washed twice with 300 mL portions of water and with saturated brine, dried over sodium sulfate, filtered and concentrated in vacuum to 2.8 g of a colorless oil. The oil was redissolved in 100 mL of methylene chloride, 3.0 g (12 mmole) of tetra-n-butylammonium borohydride added and the mixture stirred at room temperature for 15 hours. The excess reducing agent was then destroyed by the cautious addition of 200 mL of 1 N aqueous HCl, the organic phase removed in a separatory funnel, and the aqueous back-extracted with 100 mL of methylene chloride. The combined organic phases were washed with 250 mL of saturated brine, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was column chromatographed on silica gel with first methylene chloride, then 2% methanol in methylene chloride, to give 2.3 g of the (R)-enantiomer of the title compound as a colorless oil. 1H-NMR (CDCl3): doublet 7.8 δ (2H); multiplet 7.4 δ (5H); doublet 7.37 δ (2H); doublet 6.65 δ (1H); doublet 6.45 δ (1H); singlet 5.0 δ (2H); multiplet 4.43 δ (1H); multiplet 4.2 δ (3H); doublet of doublets 4.0 δ (1H); triplet 3.73 δ (2H), triplet 2.9 δ (2H); singlet 2.43 δ (3H); broad singlet 1.65 δ (1H).

Workup

  1. stirringto stir at room temperature under nitrogen for 15 hours
  2. washthe solution was washed twice with 300 mL portions of water and with saturated brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum to 2.8 g of a colorless oil
  6. dissolutionThe oil was redissolved in 100 mL of methylene chloride
  7. stirringthe mixture stirred at room temperature for 15 hours
  8. customwas then destroyed by the cautious addition of 200 mL of 1 N aqueous HCl
  9. customthe organic phase removed in a separatory funnel
  10. extractionthe aqueous back-extracted with 100 mL of methylene chloride
  11. washThe combined organic phases were washed with 250 mL of saturated brine
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuum
  15. customchromatographed on silica gel with first methylene chloride

Sources & evidence

ORD record
ord-9d67f2bc94a5409c8770cfc45a71e4d5
Source dataset
uspto-grants-2004_03
Patent number
US06706736B2

Reaction notes

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