Methanol → Ertugliflozin Impurity 11

HRID 625844ノート

反応式

HRID 625844 の反応式
[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

参加物

5

反応物 3

HCID 887MethanolHCID 6367Acetyl chlorideHCID 44814423Ertugliflozin

生成物 1

HCID 52931642Ertugliflozin Impurity 11収率 87%

試薬・触媒・溶媒 1

HCID 79532,4,6-Trimethylpyridine溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-8814eca6fdf54002bc73d8dc02348c35
出典データセット
uspto-grants-2016_04
特許番号
US09308204B2

反応ノート

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