Hydrochloric Acid → Tetrahydropyranyl ether

HRID 1704006Notes

Reaction equation

HRID 1704006 reaction equation
CS(C)=[O:3].[CH2:5]([Li])[CH2:6][CH2:7]C.Cl[CH2:11][C:12]([O-:14])=[O:13].[Li+].Cl.C[CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>O.CN(C)C=O.O1CCCC1>[O:13]1[CH2:7][CH2:6][CH2:5][CH2:11][CH:12]1[O:14][CH:18]1[CH2:19][CH2:20][CH2:21][CH2:22][O:3]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 679Dimethyl SulfoxideHCID 8058HexaneHCID 23695591Lithium chloroacetateHCID 178418339Butyllithium

Product 1

HCID 263182Tetrahydropyranyl ether

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

Refer to Chart E. There is first prepared the bis-tetrahydropyran-2-yl ether of the title compound. A solution of the formula-XLI 3,3aβ ,4,5,6,6aβ -hexahydro-5α-hydroxy-2ξ-(2'-hydroxyethyl-4β-(3'α-hydroxy-trans-1-octenyl)-2H-cyclopenta[b]furan, 3',5-bistetrahydropyran-2-yl ether (Example 5, 0.80 g.) in 10 ml. of dimethyl sulfoxide and 5 ml. of tetrahydrofuran is treated at about 0°-5° C. with 1.1 ml. of 1.6 M n-butyllithium in hexane added dropwise over a one-minute period. Thereafter the mixture is stirred at about 10° C. for 5 min., followed by additions of 8 ml. of dimethylformamide and 0.35 g. of lithium chloroacetate. The mixture is stirred at about 25° C. for 22 hr., then diluted with 125 ml. of ice and water containing 3 ml. of concentrated hydrochloric acid. The resulting mixture is extracted with dichloromethane and the organic phase is washed with cold water and brine, and concentrated. The residue containing the acid form of the formula-LIII bistetrahydropyran-2-yl ether, is converted to the methyl ester in diethyl ether by reaction with diazomethane. After 3 min., the excess diazomethane is destroyed with acetic acid and the mixture is washed with dilute potassium hydroxide solution and brine, dried, and concentrated to yield the formula-LIII bistetrahydropyran-2-yl ether of the title compound, as mixed isomers.

Workup

  1. stirringThe mixture is stirred at about 25° C. for 22 hr
  2. addition, then diluted with 125 ml
  3. extractionThe resulting mixture is extracted with dichloromethane
  4. washthe organic phase is washed with cold water and brine
  5. concentrationconcentrated
  6. additionThe residue containing the acid form of the formula-LIII bistetrahydropyran-2-yl ether
  7. customis converted to the methyl ester in diethyl ether by reaction with diazomethane
  8. waitAfter 3 min.
  9. customthe excess diazomethane is destroyed with acetic acid
  10. washthe mixture is washed with dilute potassium hydroxide solution and brine
  11. customdried
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-bff0fc9a19e34f08a49de02b1ce709cb
Source dataset
uspto-grants-1978_11
Patent number
US04125712

Reaction notes

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