Ethyl chloroformate → Carbonic acid (1R,2S,3S,4R,5S)-5-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-2,3,4-trihydoxy-6,8-dioxa-bicyclo[3.2.1]oct-1-ylmethyl ester ethyl ester

HRID 1185005

Reaktionsgleichung

Reaktionsgleichung von HRID 1185005
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]23[O:15][C@@:12]([CH2:16][OH:17])([CH2:13][O:14]2)[C@@H:11]([OH:18])[C@H:10]([OH:19])[C@H:9]3[OH:20])=[CH:4][C:3]=1[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH3:30])=[CH:24][CH:23]=1.[CH2:31]([O:33][C:34](Cl)=[O:35])[CH3:32]>N1C(C)=CC(C)=CC=1C>[CH2:31]([O:33][C:34](=[O:35])[O:17][CH2:16][C@:12]12[O:15][C@:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([CH2:21][C:22]4[CH:23]=[CH:24][C:25]([O:28][CH2:29][CH3:30])=[CH:26][CH:27]=4)[CH:4]=3)([O:14][CH2:13]1)[C@H:9]([OH:20])[C@@H:10]([OH:19])[C@@H:11]2[OH:18])[CH3:32]

Komponenten

4

Edukt 2

HCID 10928Ethyl chloroformateHCID 44814423PF-04971729

Produkt 1

HCID 52931702Carbonic acid (1R,2S,3S,4R,5S)-5-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-2,3,4-trihydoxy-6,8-dioxa-bicyclo[3.2.1]oct-1-ylmethyl ester ethyl esterAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 79532,4,6-TrimethylpyridineLösungsmittel

Versuchsvorschrift

To a vigorously stirred solution of (1S,2S,3S,4R,5S)-5-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol (1A, 288 mg, 0.659 mmol) in collidine (6.6 mL) cooled to −35 degrees Celsius was added drop-wise over 10 minutes ethylchloroformate (0.112 mL, 1.19 mmol). The reaction mixture was allowed to stir overnight at room temperature. The reaction was quenched with an aqueous solution of saturated citric acid and extracted with ethyl acetate (2 times). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography over silica gel using the biotage automated chromatography unit (50 g silica gel column) and eluting with a gradient of 0 to 20% methanol in dichloromethane. 134 mg (40% yield) of desired product as a white solid.

Aufarbeitung

  1. customThe reaction was quenched with an aqueous solution of saturated citric acid
  2. extractionextracted with ethyl acetate (2 times)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by flash chromatography over silica gel using the biotage
  8. washeluting with a gradient of 0 to 20% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-e5f8d6e622624715bc56d67036e72185
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08669380B2

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