Benzoic Acid → (3S,5S)-N-Boc-5-ethynyl-3-hydroxy-pyrrolidine

HRID 380898Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 380898
[C:1]([N:8]1[C@H:12]([C:13]#[CH:14])[CH2:11][C@@H:10]([OH:15])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(O)(=O)C1C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C([O-])([O-])=O.[K+].[K+]>C1COCC1>[C:1]([N:8]1[C@H:12]([C:13]#[CH:14])[CH2:11][C@H:10]([OH:15])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Komponenten

7

Edukt 5

HCID 243Benzoic AcidHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 11816659tert-butyl (2S,4R)-2-ethynyl-4-hydroxypyrrolidine-1-carboxylate

Produkt 1

HCID 21971746(3S,5S)-N-Boc-5-ethynyl-3-hydroxy-pyrrolidine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of (3R,5S)-N-Boc-3-Hydroxy-5-ethynyl-pyrrolidine (200 mg, 0.95 mmol) (Example 99C), benzoic acid (138 mg, 0.11 mmol) and triphenyl phosphine (373 mg, 1.42 mmol) in 15 mL of THF was added diisopropyl azodicarboxylate (287 mg, 1.42 mmol) at 0° C. The mixture was allowed to slowly warm up to room temperature and stirred for 18 hrs. The reaction mixture was then concentrated and the residue was directly passed through a silica gel column with a 0-30% EtOAc in hexanes gradient. The intermediate benzoate ester was dissolved in 6 mL of MeOH and then K2CO3 (260 mg, 1.89 mmol) was added. The mixture, after overnight stirring, was filtered and concentrated to a residue which after silica gel column chromatography with a 0-70% EtOAc in hexanes gradient afforded (3S,5S)-N-Boc-5-ethynyl-3-hydroxy-pyrrolidine. (Yield 170 mg, 85%).

Aufarbeitung

  1. concentrationThe reaction mixture was then concentrated
  2. dissolutionThe intermediate benzoate ester was dissolved in 6 mL of MeOH
  3. stirringThe mixture, after overnight stirring
  4. filtrationwas filtered
  5. concentrationconcentrated to a residue which after silica gel column chromatography with a 0-70% EtOAc in hexanes gradient

Quellen und Nachweise

ORD-Eintrag
ord-ff6fca33064c4acf91cea57b7da4aa1c
Quelldatensatz
uspto-grants-2001_10
Patentnummer
US06303793B1

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