Dichloromethane → Ethyl (S)-1-Cbz-4-oxopyrrolidine-2-carboxylate

HRID 340815

Reaktionsgleichung

Reaktionsgleichung von HRID 340815
[C:1]([N:11]1[CH2:18][C@H:17]([OH:19])[CH2:16][C@H:12]1[C:13]([OH:15])=[O:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[CH3:20][C:21](C)=O.OS(O)(=O)=O.O=[Cr](=O)=O.C(Cl)Cl.C(N1CC(=O)C[C@H]1C(O)=O)(OCC1C=CC=CC=1)=O>CC(C)=O>[CH2:20]([O:14][C:13](=[O:15])[C@@H:12]1[CH2:16][C:17](=[O:19])[CH2:18][N:11]1[C:1]([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2])[CH3:21]

Komponenten

6

Edukt 4

HCID 6344DichloromethaneHCID 3915171-(Phenylmethyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylateHCID 11076282N-Carbobenzyloxy-4-keto-L-prolineHCID 131709961Jones' reagent

Produkt 1

HCID 14540986Ethyl (S)-1-Cbz-4-oxopyrrolidine-2-carboxylateAusbeute 71 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 180AcetoneLösungsmittel

Versuchsvorschrift

To a round bottom flask containing 14.0 g (52.8 mmol) of N-Cbz-4-hydroxy-L-proline 8 was added 26 mL acetone. The solution was cooled on ice bath where 8.12 mL (0.106 mmol; 2 eq) of Jones reagent (CrO3, H2SO4, 1.3 M in water) was added. The mixture was allowed to warm to room temperature and stir for 3 h where the reaction appeared to be complete, as determined by TLC. The reaction was quenched by the addition of 6 mL isopropanol. After stirring for another 2 h the flask was placed on a glass socket rotovap and the isopropanol/acetone was removed by reduced pressure. The remaining green residue was then diluted into 200 mL water, salted with NaCl and extracted with EtOAc (3×200 mL). The organic extracts were combined, dried with MgSO4, filtered and concentrated to an oil. The remaining yellow oil was then separated by silica gel (90% CH2Cl2, 9% MeOH, 1% AcOH, Rf=0.3). The fractions containing the product were combined and concentrated by rotovap to a solid residue and then recrystallized from CH2Cl2 leaving 9.86 g (37.5 mmol) of N-Cbz-4-keto-L-proline, a 71% yield. The product material was used in the next synthetic step without further purification.

Aufarbeitung

  1. additionwas added
  2. customThe reaction was quenched by the addition of 6 mL isopropanol
  3. stirringAfter stirring for another 2 h the flask
  4. customthe isopropanol/acetone was removed by reduced pressure
  5. additionThe remaining green residue was then diluted into 200 mL water
  6. extractionextracted with EtOAc (3×200 mL)
  7. dry with materialdried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to an oil
  10. customThe remaining yellow oil was then separated by silica gel (90% CH2Cl2, 9% MeOH, 1% AcOH, Rf=0.3)
  11. additionThe fractions containing the product
  12. concentrationconcentrated by rotovap to a solid residue
  13. customThe product material was used in the next synthetic step without further purification

Quellen und Nachweise

ORD-Eintrag
ord-a00ca602304b49e2b0dabbd4e1221609
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08895607B2

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