Water → Tetrahydropyranyl ether

HRID 1414431Notes

Reaction equation

HRID 1414431 reaction equation
[H-].[Na+].[PH4+].[Br-].F[C:6](F)([CH2:28][C:29]([OH:31])=[O:30])[CH2:7][CH2:8][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.S(=O)(=O)(O)[O-].[K+].[OH2:39]>C1C=CC=CC=1.CS(C)=O>[O:39]1[CH2:29][CH2:28][CH2:6][CH2:7][CH:8]1[O:31][CH:29]1[CH2:28][CH2:6][CH2:7][CH2:8][O:30]1

Participants

8

Reactant 5

HCID 962WaterHCID 24758Sodium hydrideHCID 516920Potassium bisulfateHCID 5460504PhosphoniumHCID 21188198HCID 21188198, compound

Product 1

HCID 263182Tetrahydropyranyl ether

Reagents, catalysts & solvents 2

HCID 241BenzeneSolvent3×HCID 679Dimethyl SulfoxideSolvent2×

Procedure

The free acid prepared from the lactol of Preparation 95 which is of the same epimeric configuration at the 3 position of its side chain as the desired configuration at C-15 position of the prostaglandin-type product of this example. The reaction of this part is carried out under an atmosphere of nitrogen with exclusion of moisture. 20 ml. of dimethyl sulfoxide is added to 0.88 g. of a 50 percent sodium hydride dispersion in mineral oil. The mixture is stirred and heated at 70° to 80° C. for 1 hour, then cooled in an ice bath. 4.4 g. of the phosphonium salt of Example A, (3,3-difluoro-4-carboxybutyl)triphenylphosphonium bromide, is added with stirring. The ice bath is removed and stirring is continued for 15 min. 2 g. of the lactol of Preparation 95 dissolved in 5 ml. of dimethyl sulfoxide and 5 ml. of benzene is added dropwise, followed by 10 ml. of benzene. Stirring is continued for 1.5 hr. The reaction mixture is then diluted with 200 ml. of benzene and a solution of 3 g. of potassium bisulfate in 75 ml. of water. The layers are separated and the aqueous layer is extracted twice with 100 ml. of benzene. The organic solutions are combined and washed twice with 50 ml. of water. The water is backwashed with 100 ml. of benzene, and the combined benzene solutions are then dried over sodium sulfate. Filtration and evaporation of solvent yields the bis-tetrahydropyranyl ether of 2,2-difluoro-PGF2α.

Workup

  1. customThe reaction of this part
  2. temperatureheated at 70° to 80° C. for 1 hour
  3. temperaturecooled in an ice bath
  4. stirringwith stirring
  5. customThe ice bath is removed
  6. stirringstirring
  7. customof the lactol of Preparation 95
  8. dissolutiondissolved in 5 ml
  9. stirringStirring
  10. waitis continued for 1.5 hr
  11. additionThe reaction mixture is then diluted with 200 ml
  12. customThe layers are separated
  13. extractionthe aqueous layer is extracted twice with 100 ml
  14. washwashed twice with 50 ml
  15. dry with materialof benzene, and the combined benzene solutions are then dried over sodium sulfate
  16. filtrationFiltration and evaporation of solvent

Sources & evidence

ORD record
ord-6823fead2b374a9bbbd843c17b30bf0f
Source dataset
uspto-grants-1977_01
Patent number
US04001300

Reaction notes

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