Dichloromethane → HCID 70220435, compound

HRID 568269Notes

Reaction equation

HRID 568269 reaction equation
S(Cl)(Cl)=[O:2].[CH2:5]([O:8][C:9]([N:11]1[C@H:15]([CH:16](O)[C:17]2[N:24]3[C:20]([S:21][CH:22]=[CH:23]3)=[CH:19][N:18]=2)[C:14](C)(C)[C@@H:13](C(C)(C)C)[CH:12]1O[SiH3])=[O:10])[CH:6]=[CH2:7].ClCCl>CN(C=O)C.C(O)(=O)C.[Zn]>[CH2:5]([O:8][C:9]([N:11]1[C@H:15]([CH2:16][C:17]2[N:24]3[C:20]([S:21][CH:22]=[CH:23]3)=[CH:19][N:18]=2)[CH2:14][C@@H:13]([OH:2])[CH2:12]1)=[O:10])[CH:6]=[CH2:7]

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 24386Thionyl ChlorideHCID 131722373HCID 131722373, compound

Product 1

HCID 70220435HCID 70220435, compound

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

Thionyl chloride (0.39 ml) is added to a solution of 774 mg of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethyl-silyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-5-yl)methyl]pyrrolidine (stereoisomer A) in 0.014 ml of dry DMF and 5.3 ml of dry dichloromethane under ice cooling, and the mixture is stirred in this state for 25 min. The solvent and the excess reagent are removed by evaporation under reduced pressure, and the residue is dried under reduced pressure by means of a vacuum pump to give a bright yellow amorphous material which is then dissolved in 17.7 ml of 90% acetic acid. Zinc (1.156 g) is added to the solution under ice cooling, and the mixture is stirred in this state for 20 min. Further, the ice bath is removed, and stirring is continued for additional 10 min. Distilled water and ethyl acetate are added, and the mixture adjusted to pH 6 under stirring by addition of sodium hydrogencarbonate. The organic layer is separated, and the residual aqueous layer is adjusted to pH 8 by addition of sodium hydrogencarbonate, followed by extraction with ethyl acetate. The combined organic layers are washed twice with an 5% aqueous sodium hydrogencarbonate solution, dried over magnesium sulfate and potassium carbonate and filtered. The solvent is removed by evaporation under reduced pressure. The residue, together with acetonitrile, is once subjected to azeotropic evaporation, the residue is redissolved in 17.7 ml of acetonitrile, 0.70 ml of concentrated hydrochloric acid is added thereto under ice cooling, and the mixture is stirred in this state for 15 min. The mixture is diluted with 200 ml of ethyl acetate, the diluted solution is washed with 50 ml of a 5% aqueous sodium hydrogencarbonate solution, the organic layer is dried over magnesium sulfate, filtered, and the solvent is removed by evaporation under reduced pressure to give a yellowish orange amorphous material. The amorphous material is successively purified by column chromatography on silica gel (first, ethyl acetate:methanol=9:1; second, chloroform:methanol 9:1) and on Sephadex LH-20 (chloroform:methanol=1:1) to give 138 mg of (3R,5R)-1-allyloxycarbonyl-3-hydroxy-5-(imidazo[5,1-b]thiazol-5-yl)methylpyrrolidine as a colorless amorphous material.

Workup

  1. customThe solvent and the excess reagent are removed by evaporation under reduced pressure
  2. customthe residue is dried under reduced pressure by means of a vacuum pump
  3. customto give a bright yellow amorphous material which
  4. customFurther, the ice bath is removed
  5. stirringstirring
  6. waitis continued for additional 10 min
  7. additionDistilled water and ethyl acetate are added
  8. stirringunder stirring by addition of sodium hydrogencarbonate
  9. customThe organic layer is separated
  10. additionthe residual aqueous layer is adjusted to pH 8 by addition of sodium hydrogencarbonate
  11. extractionfollowed by extraction with ethyl acetate
  12. washThe combined organic layers are washed twice with an 5% aqueous sodium hydrogencarbonate solution
  13. dry with materialdried over magnesium sulfate and potassium carbonate
  14. filtrationfiltered
  15. customThe solvent is removed by evaporation under reduced pressure
  16. customThe residue, together with acetonitrile, is once subjected to azeotropic evaporation
  17. dissolutionthe residue is redissolved in 17.7 ml of acetonitrile
  18. addition0.70 ml of concentrated hydrochloric acid is added
  19. stirringunder ice cooling, and the mixture is stirred in this state for 15 min
  20. additionThe mixture is diluted with 200 ml of ethyl acetate
  21. washthe diluted solution is washed with 50 ml of a 5% aqueous sodium hydrogencarbonate solution
  22. dry with materialthe organic layer is dried over magnesium sulfate
  23. filtrationfiltered
  24. customthe solvent is removed by evaporation under reduced pressure
  25. customto give a yellowish orange amorphous material
  26. customThe amorphous material is successively purified by column chromatography on silica gel (first, ethyl acetate

Sources & evidence

ORD record
ord-ec1204588097497aa6dcaa889c9fdbd7
Source dataset
uspto-grants-2001_01
Patent number
US06180622B2

Reaction notes

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