Benzyl Bromide → [[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phen yl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]tert-butyl-dimethyl-silane

HRID 1055550노트

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HRID 1055550 반응식
[H-].[Na+].[Si:3]([O:10][CH2:11][C@H:12]1[O:17][C@:16]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]([F:39])([F:38])[F:37])=[CH:30][CH:29]=3)[CH:21]=2)([O:18][CH3:19])[C@H:15]([OH:40])[C@@H:14]([OH:41])[C@@H:13]1[OH:42])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].[CH2:43](Br)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>O1CCCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:6]([Si:3]([CH3:5])([CH3:4])[O:10][CH2:11][C@@H:12]1[C@@H:13]([O:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C@H:14]([O:41][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:15]([O:40][CH2:16][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@@:16]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]([F:39])([F:38])[F:37])=[CH:30][CH:29]=3)[CH:21]=2)([O:18][CH3:19])[O:17]1)([CH3:8])([CH3:9])[CH3:7]

참가 물질

6

반응물 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 86685148(2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxy-methyl]-2-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol

생성물 1

HCID 86685149[[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phen yl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]tert-butyl-dimethyl-silane수율 46.1%

시약·촉매·용매 2

HCID 67553Tetrabutylammonium Iodide촉매HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

To a suspension of sodium hydride (1.90 g, 47.4 mmol, 60% dispersion in Mineral oil) in anhydrous tetrahydrofuran (50 mL) was added a solution of (2S,3R,4S,5S,6R)-6-[[tert-butyl (dimethyl)silyl]oxymethyl]-2-[4-chloro-3-[[4-(2,2,2-trifluoro ethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahy dropyran-3,4,5-triol 17f (4.8 g, 7.91 mmol) in anhydrous tetrahydrofuran (50 mL) slowly at 0° C. The mixture was stirred at 0° C. for 1 hour and warmed to room temperature. Then benzyl bromide (5.6 mL, 47.4 mmol) and tetrabutylammonium iodide (0.3 g, 0.79 mmol) were added in turn. The mixture was warmed up to 40° C. and further stirred for 12 hours. The reaction mixture was quenched with water (50 mL) and partitioned. The aqueous layer was extracted with ethyl acetate (50 mL×2). The combined organic layers were washed with saturated brine (80 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=20/1 to give the title compound 17g as orange-yellow oil (1.6 g, 23.0%). This material was not further purified.

후처리

  1. temperaturewarmed to room temperature
  2. temperatureThe mixture was warmed up to 40° C.
  3. stirringfurther stirred for 12 hours
  4. customThe reaction mixture was quenched with water (50 mL)
  5. custompartitioned
  6. extractionThe aqueous layer was extracted with ethyl acetate (50 mL×2)
  7. washThe combined organic layers were washed with saturated brine (80 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated in vacuo
  11. customthe residue was purified by silica gel chromatography
  12. washeluted with PE/EtOAc(v/v)=20/1

출처 및 근거

ORD 기록
ord-753e770c2d8a4a889bd1aa5bb6e6b525
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394329B2

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