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 59193

反応式

HRID 59193 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.[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]

参加物

4

反応物 2

HCID 10928Ethyl chloroformateHCID 44814423PF-04971729

生成物 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 ester収率 40%

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, 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.

後処理

  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

出典と根拠

ORDレコード
ord-226e397de7a04e5a983c2f4e8450b8b5
出典データセット
uspto-grants-2016_09
特許番号
US09439901B2

関連ノート

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