Water → Acetic acid 2-{4-[2-chloro-5-((1S,2S,3S,4R,5S)-2,3,4-trihydroxy-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]oct-5-yl)-benzyl]-phenoxy}-ethyl ester

HRID 1185006

반응식

HRID 1185006 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]([OH:28])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:36][CH2:37][O:38][C:39](=[O:41])[CH3:40].O>C(#N)C.C(OCC)(=O)C>[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:23]=[CH:24][C:25]([O:28][CH2:36][CH2:37][O:38][C:39](=[O:41])[CH3:40])=[CH:26][CH:27]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 135641-Acetoxy-2-bromoethane2회HCID 67153906(1S,2S,3S,4R,5S)-5-[4-chloro-3-(4-hydroxy-benzyl)-phenyl]-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol

생성물 1

HCID 52931703Acetic acid 2-{4-[2-chloro-5-((1S,2S,3S,4R,5S)-2,3,4-trihydroxy-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]oct-5-yl)-benzyl]-phenoxy}-ethyl ester수율 22%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of (1S,2S,3S,4R,5S)-5-[4-chloro-3-(4-hydroxy-benzyl)-phenyl]-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol (38 mg, 0.093 mmol) in acetonitrile (0.9 mL) was added potassium carbonate (40 mg, 0.28 mmol) followed by the addition of acetic acid 2-bromo-ethyl ester (0.012 mL, 0.112 mmol) and the resulting mixture was heated to 50 degrees Celsius for 72 hours. The reaction showed some product formation but the majority of starting material remained. An additional 2 equivalents of acetic acid 2-bromo-ethyl ester was added and the mixture was heated at 50 degrees Celsius for an additional 24 hours. Water (20 mL) and ethyl acetate were added, the two phases separated and the aqueous phase was extracted 3 times with ethyl acetate (20 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography over silica gel using the ISCO automated chromatography unit (4 g silica gel column) and eluting with a gradient of 0 to 30% methanol in dichloromethane. 10 mg (22% yield) of a ˜2:1 mixture of the desired product contaminated with some unidentified compound was obtained. LCMS 539 M+HCOO−, negative mode).

후처리

  1. temperaturethe resulting mixture was heated to 50 degrees Celsius for 72 hours
  2. temperaturethe mixture was heated at 50 degrees Celsius for an additional 24 hours
  3. customthe two phases separated
  4. extractionthe aqueous phase was extracted 3 times with ethyl acetate (20 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by flash chromatography over silica gel using the ISCO automated chromatography unit (4 g silica gel column)
  10. washeluting with a gradient of 0 to 30% methanol in dichloromethane
  11. addition10 mg (22% yield) of a ˜2:1 mixture of the desired product
  12. customwas obtained

출처 및 근거

ORD 기록
ord-e1cff312873d4072aa0cb544bda8b2b0
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08669380B2

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