Ethyl Acetate → (3R*,4R*)-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

HRID 1972089Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1972089
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH:12]2[CH:10]([O:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N-:15]=[N+:16]=[N-:17].[Na+].CCOC(C)=O>CN(C=O)C.CC(C)=O.O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C@@H:12]([N:15]=[N+:16]=[N-:17])[C@H:10]([OH:11])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

6

Edukt 3

HCID 8857Ethyl AcetateHCID 33557Sodium AzideHCID 21991116tert-Butyl 7-Oxa-3-azabicyclo(4.1.0)heptane-3-carboxylate

Produkt 1

HCID 58745530(3R*,4R*)-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl esterAusbeute 61,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 18366337Propan-2-one--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a stirred solution of 7-oxa-3-aza-bicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl ester (15.5 mmol, 3.1 g) in DMF (25 mL) was added a solution of sodium azide (23.3 mmol, 1.5 g) in acetone-water (2:1, 30 mL) (WO 2005/066176). The reaction mixture was heated at 80° C. for 12 h. The reaction mixture was cooled to room temperature, and EtOAc (100 mL) was added. The organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on a SiO2 cartridge (5% EtOAc in hexane -25% EtOAc in hexane) to provide (±)-trans-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (2.3 g)(faster moving compound) 1H NMR (400 MHz, CDCl3) δ 4.12 (1H, dd), 3.95 (1H, bs), 3.50 (1H, bs), 3.30-3.42 (1H, m), 2.90 (1H, bs), 2.79 (1H, dd), 2.30-2.70 (1H, bs), 1.96-2.05 (1H, m), 1.48-1.6 (1H, m), 1.46 (9H, s). and (±)-trans-3-azido-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.57 g) (slower moving compound) 1H NMR (400 MHz, CDCl3) δ 4.21 (1H, bs), 4.00 (1H, d), 3.56 (1H, bs), 3.21-3.35 (1H, m), 2.55-2.95 (2H, m), 2.24 (1H, bs), 1.92-2.04 (1H, m), 1.49-1.6 (1H, m), 1.47 (9H, s)

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified on a SiO2 cartridge (5% EtOAc in hexane -25% EtOAc in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-3e2f7dcc573e4eebbccdc73acf1d199c
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08431575B2

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