Benzyl Alcohol → 1-Tert-butyloxycarbonyl-trans-3-benzyloxycarbonylamino-4-(2-pyridyl)pyrrolidine

HRID 398399Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 398399
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C@H:10](C(O)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC[N:24]([CH:28](C)C)C(C)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:38])C=CC=CC=1.[CH2:48]([OH:55])[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>C1(C)C=CC=CC=1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C@H:10]([NH:24][C:28]([O:55][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)=[O:38])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Komponenten

7

Edukt 4

HCID 244Benzyl AlcoholHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 2762196Boc-trans-4-(2-pyridinyl)-pyrrolidine-3-carboxylic acid

Produkt 1

HCID 700235531-Tert-butyloxycarbonyl-trans-3-benzyloxycarbonylamino-4-(2-pyridyl)pyrrolidine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a stirred solution of 1-tert-butyloxycarbonyl-trans-4-(2-pyridyl)pyrrolidine-3-carboxylic acid from step 5 above (13 mmol) in toluene (50 mL) was added DIEA (3.0 mL, 17 mmol). The solution was cooled to 0° C. and diphenylphosphoryl azide (4.1 g, 15 mmol) was added. The resulting solution was stirred at 0° C. for 1 h and at ambient temperature for 4 h. Benzyl alcohol (2.8 g, 26 mmol) was added and the solution was refluxed for 3 h. The solution was cooled to ambient temperature, diluted with EtOAc, and washed with aqueous NaHCO3. The organic phase was separated, dried over MgSO4, filtered, and the solvents were removed in vacuo. The residue was purified by flash column chromatography using a gradient elution of 10-25% EtOAc:hexanes to give the title compound as an oil (3.9 g, TLC Rf=0.4, 1:3 EtOAc-hexanes; HPLC RT=6.67 min, method A).

Aufarbeitung

  1. temperaturethe solution was refluxed for 3 h
  2. temperatureThe solution was cooled to ambient temperature
  3. washwashed with aqueous NaHCO3
  4. customThe organic phase was separated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe solvents were removed in vacuo
  8. customThe residue was purified by flash column chromatography
  9. washa gradient elution of 10-25% EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-e8b46c32a3784204809afd97ef45b796
Quelldatensatz
uspto-grants-2003_08
Patentnummer
US06610692B1

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