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 1055550Notes

Reaction equation

HRID 1055550 reaction equation
[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]

Participants

6

Reactant 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

Product 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-silaneYield 46.1%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-753e770c2d8a4a889bd1aa5bb6e6b525
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

Loading…