Ethyl Acetate → 2-(2-phenyltetrahydro-2H-pyran-2-yl)acetaldehyde

HRID 71263Notes

Reaction equation

HRID 71263 reaction equation
[CH2:1]([C:4]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:9][CH2:8][CH2:7][CH2:6][O:5]1)[CH:2]=C.C[N+]1([O-])CC[O:20]CC1.I([O-])(=O)(=O)=O.[Na+].CCOC(C)=O>C1COCC1.O.CO.O=[Os](=O)(=O)=O>[C:10]1([C:4]2([CH2:1][CH:2]=[O:20])[CH2:9][CH2:8][CH2:7][CH2:6][O:5]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 82029Methyl morpholine oxideHCID 23667635Sodium periodateHCID 666850742-allyl-2-phenyltetrahydro-2H-pyran

Product 1

HCID 866882052-(2-phenyltetrahydro-2H-pyran-2-yl)acetaldehydeYield 64%

Reagents, catalysts & solvents 4

HCID 30318Osmium TetroxideCatalystHCID 887MethanolSolventHCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-allyl-2-phenyltetrahydro-2H-pyran (370 mg, 1.829 mmol, Preparation 14B) in THF (2.5 mL) was added a solution of N-methylmorpholine-N-oxide (321 mg, 2.74 mmol) in water (2.5 mL), and then 0.37 mL of 2.5% OsO4 in water was also added. The mixture was stirred at room temperature for 1 day. The reaction was quenched with aq Na2S2O3 and the product was extracted with EtOAc. The extract was washed with brine, and the combined aqueous layers were back extracted with EtOAc once and combined. The extracts were dried over Na2SO4 and evaporated to give an oily residue. The residue was dissolved in MeOH (5 mL). A solution of sodium periodate (469 mg, 2.195 mmol) in water (5 mL) was added dropwise at 0° C. As soon as the addition started, white precipitate formed. The mixture was stirred for 30 mins at the same temperature and poured into EtOAc. The extract was washed with brine, and the combined aqueous layers were back extracted with EtOAc and combined. The extracts were dried over Na2SO4 and evaporated to give an oily residue. The residue was purified by Combiflash (40 g silica gel) eluting with 1:9 EtOAc-hexane to give 2-(2-phenyltetrahydro-2H-pyran-2-yl)acetaldehyde as an oil (239 mg). 1H NMR (400 MHz, CCl3D) δ ppm 9.64-9.68 (1H, m), 7.36-7.46 (4H, m), 7.25-7.31 (1H, m), 3.74-3.81 (1H, m), 3.55-3.64 (1H, m), 2.58-2.75 (2H, m), 2.29-2.39 (1H, m), 1.80-1.92 (1H, m), 1.59-1.75 (2H, m), 1.40-1.58 (2H, m).

Workup

  1. customThe reaction was quenched with aq Na2S2O3
  2. extractionthe product was extracted with EtOAc
  3. washThe extract was washed with brine
  4. extractionthe combined aqueous layers were back extracted with EtOAc once
  5. dry with materialThe extracts were dried over Na2SO4
  6. customevaporated
  7. customto give an oily residue
  8. additionAs soon as the addition
  9. customwhite precipitate formed
  10. stirringThe mixture was stirred for 30 mins at the same temperature
  11. washThe extract was washed with brine
  12. extractionthe combined aqueous layers were back extracted with EtOAc
  13. dry with materialThe extracts were dried over Na2SO4
  14. customevaporated
  15. customto give an oily residue
  16. customThe residue was purified by Combiflash (40 g silica gel)
  17. washeluting with 1:9 EtOAc-hexane

Sources & evidence

ORD record
ord-03c0aefab19e4b8b8cc6f93519b5553f
Source dataset
uspto-grants-2014_09
Patent number
US08822510B2

Reaction notes

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