Potassium Phosphate, Dibasic → (3aR,6aR)-tetrahydrofuro[2,3-b]furan-3(2H)-one

HRID 553266Notes

Reaction equation

HRID 553266 reaction equation
[O:1]1[C@H:5]2[O:6][CH2:7][CH2:8][C@H:4]2[C@@H:3]([OH:9])[CH2:2]1.O1[C@H]2OCC[C@H]2[C@H](O)C1.P([O-])([O-])(O)=O.[K+].[K+].Cl[O-].[Na+]>C(OCC)(=O)C.O1[C@@H]2OCC[C@@H]2[C@H](O)C1.O1[C@@H]2OCC[C@@H]2[C@@H](O)C1.[Br-].[K+].CC(O)C>[O:1]1[C@H:5]2[O:6][CH2:7][CH2:8][C@H:4]2[C:3](=[O:9])[CH2:2]1

Participants

10

Reactant 4

HCID 24450Potassium Phosphate, DibasicHCID 9942150(3R,3aS,6aR)-hexahydrofuro(2,3-b)furan-3-olHCID 11147731(3S,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-olHCID 23665760Sodium Hypochlorite

Product 1

HCID 10678248(3aR,6aR)-tetrahydrofuro[2,3-b]furan-3(2H)-oneYield 94.8%

Reagents, catalysts & solvents 5

HCID 253877Potassium BromideCatalystHCID 10374488(3s,3ar,6as)-Hexahydrofuro[2,3-B]furan-3-OlCatalystHCID 11819104(3R,3aR,6aS)-Hexahydrofuro[2,3-b]furan-3-olCatalystHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

The mixture (18.9 g) containing (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol (7.93 g, 60.9 mmol), (3S,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol (2.07 g, 15.9 mmol), (3S,3aR,6aS)-hexahydrofuro[2,3-b]furan-3-ol (0.05 g, 0.4 mmol) and (3R,3aR,6aS)-hexahydrofuro[2,3-b]furan-3-ol (0.05 g, 0.4 mmol) obtained in Example 4 was dissolved in ethyl acetate (112 ml), and dipotassium hydrogen phosphate (27.1 g, 155.3 mmol), potassium bromide (0.5 g, 3.9 mmol) and 2,2,6,6-tetramethylpiperidinyl-1-oxy (61 mg, 0.4 mmol) were added, and the mixture was cooled to 0. Into this was dropped a sodium hypochlorite aqueous solution (123.9 g, effective chlorine concentration 14%, 0.23 mol) at 15° C. or less, and after completion of dropping, the mixture was stirred for 1 hour. After completion of the reaction, 2-propanol (10 ml) was added, and the mixture was stirred for 30 minutes and liquid-partitioned. Further, the aqueous layer was extracted with ethyl acetate (50 ml) and the organic layers were combined, and dried over anhydrous sodium sulfate (1.0 g) added. Sodium sulfate was filtrated, then, the solvent was distilled off, and 2-propanol (30 ml) was added to the concentrated residue and recrystallization was performed, to obtain a pale brown white crystal (3aR,6aR)-tetrahydrofuro[2,3-b]furan-3(2H)-one (7.4 g, purity 98%, yield 73%). At this stage, the enantiomer excess was 100% ee.

Workup

  1. temperaturethe mixture was cooled to 0
  2. additionwas added
  3. stirringthe mixture was stirred for 30 minutes
  4. customliquid-partitioned
  5. extractionFurther, the aqueous layer was extracted with ethyl acetate (50 ml)
  6. dry with materialdried over anhydrous sodium sulfate (1.0 g)
  7. additionadded
  8. filtrationSodium sulfate was filtrated
  9. distillationthe solvent was distilled off
  10. addition2-propanol (30 ml) was added to the concentrated residue and recrystallization

Sources & evidence

ORD record
ord-10a29a30309f49cd9c63dccf3ef2bef2
Source dataset
uspto-grants-2011_05
Patent number
US07951977B2

Reaction notes

Loading…