Methanol → Ertugliflozin Impurity 11

HRID 59212Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 59212
[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.[C:31](Cl)(=[O:33])[CH3:32].CO>N1C(C)=CC(C)=CC=1C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]23[O:15][C@@:12]([CH2:16][O:17][C:31](=[O:33])[CH3:32])([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:23]=[CH:24][C:25]([O:28][CH2:29][CH3:30])=[CH:26][CH:27]=1

Komponenten

5

Edukt 3

HCID 887MethanolHCID 6367Acetyl chlorideHCID 44814423Ertugliflozin

Produkt 1

HCID 52931642Ertugliflozin Impurity 11Ausbeute 87 %

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, 0.481 g, 1.1 mmol) in collidine (2.5 mL) cooled to −35 degrees Celsius was added drop-wise over 10 minutes acetyl chloride (0.149 mL, 2.1 mmol). After 1 hour, methanol (0.5 mL) was added and the reaction mixture was allowed to warm to room temperature. The crude mixture was concentrated under reduced pressure and codistilled three times with toluene. 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 15% methanol in dichloromethane. 456 mg (87% yield) of product obtained as a white solid.

Aufarbeitung

  1. concentrationThe crude mixture was concentrated under reduced pressure
  2. customThe crude material was purified by flash chromatography over silica gel using the biotage
  3. washeluting with a gradient of 0 to 15% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-43ed82097a2f4b8e9ddeac81dbdf91d5
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09439902B2

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