Reaktion #89679

ord-d7769027eaee4b8bba14277128aded74

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    workup.STIRRINGthe resulting homogeneous mixture was stirred at room temperature for 3.5 h
  2. 2
    Waschenwashed successively with water (2×20 mL), saturated aqueous NaHCO3 (2×20 mL) and saturated aqueous sodium chloride
  3. 3
    Trocknendried over Na2SO4
  4. 4
    Einengenconcentrated
  5. 5
    SonstigePurification by silica gel chromatography (90 g column, 15-35% ethyl acetate in hexanes)

Vorschrift

A mixture of N-(tert-butoxycarbonyl)-4-(trifluoromethyl)phenylalanine (268 mg, 0.804 mmol), 1-hydroxybenzotriazole hydrate (123 mg, 0.804 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (154 mg, 0.804 mmol) in dry methylene chloride (10 mL) and DMF (3 mL) was stirred at room temperature. After 1 h, a second solution of racemic 2-oxo-2-phenylethyl (3R,4S)-3-azido-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl]pyrrolidine-3-carboxylate hydrochloride (350 mg, 0.73 mmol) in methylene chloride (3.5 mL) was added, followed immediately by Et3N (204 uL, 1.46 mmol), and the resulting homogeneous mixture was stirred at room temperature for 3.5 h. Once complete, the mixture was diluted with dichloromethane (8 mL), washed successively with water (2×20 mL), saturated aqueous NaHCO3 (2×20 mL) and saturated aqueous sodium chloride, dried over Na2SO4 and concentrated. Purification by silica gel chromatography (90 g column, 15-35% ethyl acetate in hexanes) gave 2-oxo-2-phenylethyl (3R,4S)-3-azido-1-[N-(tert-butoxycarbonyl)-4-(trifluoromethyl)phenylalanyl]-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl]pyrrolidine-3-carboxylate (233 mg, ˜60% purity) as a white foam which was used without further purification. LC-MS ESI+MS found for C37H47BF3N5O8 m/z 758.3 (M+H), 780.3 (M+Na); ESI−MS m/z 756.5 (M−H).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US09440995B2uspto-grants-2016_09