Methanol → Ertugliflozin Impurity 11

HRID 625844노트

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HRID 625844 반응식
[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

참가 물질

5

반응물 3

HCID 887MethanolHCID 6367Acetyl chlorideHCID 44814423Ertugliflozin

생성물 1

HCID 52931642Ertugliflozin Impurity 11수율 87%

시약·촉매·용매 1

HCID 79532,4,6-Trimethylpyridine용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-8814eca6fdf54002bc73d8dc02348c35
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09308204B2

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