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

HRID 1055571Notes

Reaction equation

HRID 1055571 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][CH3:35])=[C:30]([F:36])[C:29]=3[F:37])[CH:21]=2)([O:18][CH3:19])[C@H:15]([OH:38])[C@@H:14]([OH:39])[C@@H:13]1[OH:40])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].[CH2:41](Br)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>O1CCCC1>[C:6]([Si:3]([CH3:5])([CH3:4])[O:10][CH2:11][C@@H:12]1[C@@H:13]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C@H:14]([O:39][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:15]([O:38][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][CH3:35])=[C:30]([F:36])[C:29]=3[F:37])[CH:21]=2)([O:18][CH3:19])[O:17]1)([CH3:8])([CH3:9])[CH3:7]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 131736387(2S,3R,4S,5S,6R)-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol

Product 1

HCID 131736388tert-butyl-dimethyl-[[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]silaneYield 200%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (24.0 g, 0.6 mol, 60% dispersion in Mineral oil) in anhydrous tetrahydrofuran (150 mL) was added a solution of (2S,3R,4S,5S,6R)-6-[[tert-butyhdimethyl) silyl]oxymethyl]-2-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol 21i (49.5 g, 86 mmol) in anhydrous tetrahydrofuran (400 mL) slowly at 0° C. The mixture was stirred at 0° C. for 1 hour, and then benzyl bromide (81 mL, 690 mmol) was added. The mixture was warmed up to room temperature and further stirred for 12 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride (1000 mL) and extracted with ethyl acetate (300 mL×2). The combined organic layers were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to give the title compound 21j as yellow oil (72.7 g, 100%). This material was not further purified.

Workup

  1. temperatureThe mixture was warmed up to room temperature
  2. stirringfurther stirred for 12 hours
  3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride (1000 mL)
  4. extractionextracted with ethyl acetate (300 mL×2)
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-30d2f7f1d023452fa7f632a82beb4218
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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