Oxalyl chloride → (S)-2-(((S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)pyrrolidine-2-carbonyl)oxy)propanoic acid

HRID 1482281Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1482281
C(Cl)(=O)C(Cl)=O.[CH:7]1[C:19]2[CH:18]([CH2:20][O:21][C:22]([N:24]3[CH2:28][CH2:27][CH2:26][C@H:25]3[C:29]([OH:31])=[O:30])=[O:23])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]=2[CH:10]=[CH:9][CH:8]=1.C(N(C(C)C)C(C)C)C.[C:41]([OH:46])(=[O:45])[C@H:42]([CH3:44])O>C(Cl)Cl.CN(C)C=O>[CH:16]1[C:17]2[CH:18]([CH2:20][O:21][C:22]([N:24]3[CH2:28][CH2:27][CH2:26][C@H:25]3[C:29]([O:31][C@@H:42]([CH3:44])[C:41]([OH:46])=[O:45])=[O:30])=[O:23])[C:19]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:12]=2[CH:13]=[CH:14][CH:15]=1

Komponenten

7

Edukt 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 107689L-Lactic AcidHCID 688135Fmoc-Pro-OH

Produkt 1

HCID 89668668(S)-2-(((S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)pyrrolidine-2-carbonyl)oxy)propanoic acidAusbeute 71,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Oxalyl chloride (2.34 mL, 26.7 mmol) was added dropwise to a solution of (S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)pyrrolidine-2-carboxylic acid (Fmoc-Pro-OH) (6.00 g, 17.8 mmol) and N,N-dimethylformamide (69 μL, 0.889 mmol) in methylene chloride (71 mL) with stirring at 0° C. under a nitrogen atmosphere, and the reaction mixture was then stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, the resulting residue was mixed with methylene chloride (71 mL), N-ethyldiisopropylamine (DIPEA) (46.6 mL, 267 mmol) and L-(+)-lactic acid (24.0 g, 267 mmol) at 0° C., and the reaction mixture was stirred at room temperature for 2 hours. The reaction solution was washed with 1 N hydrochloric acid twice and a saturated aqueous sodium chloride solution twice, dried over sodium sulfate and then concentrated under reduced pressure. The resulting residue was purified by reverse-phase silica gel column chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution) to afford (S)-2-(((S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)pyrrolidine-2-carbonyl)oxy)propanoic acid (Fmoc-Pro-Lac-OH) (Compound SP633) (5.2 g, 12.7 mmol, 71%).

Aufarbeitung

  1. stirringthe reaction mixture was then stirred at room temperature for 1 hour
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. stirringthe reaction mixture was stirred at room temperature for 2 hours
  4. washThe reaction solution was washed with 1 N hydrochloric acid twice
  5. dry with materiala saturated aqueous sodium chloride solution twice, dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by reverse-phase silica gel column chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution)

Quellen und Nachweise

ORD-Eintrag
ord-7c45124ff9ed42c293c34c0ff62ad338
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09409952B2

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