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

HRID 1055535Notes

Reaction equation

HRID 1055535 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[O:15][C@:14]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]([F:36])([F:35])[F:34])=[CH:28][CH:27]=3)[CH:19]=2)([O:16][CH3:17])[C@H:13]([OH:37])[C@@H:12]([OH:38])[C@@H:11]1[OH:39])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].[CH2:42](Br)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>O1CCCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:4]([Si:1]([CH3:3])([CH3:2])[O:8][CH2:9][C@@H:10]1[C@@H:11]([O:39][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C@H:12]([O:38][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@@H:13]([O:37][CH2:14][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@:14]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]([F:36])([F:35])[F:34])=[CH:28][CH:27]=3)[CH:19]=2)([O:16][CH3:17])[O:15]1)([CH3:6])([CH3:7])[CH3:5]

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 86685138(2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxymethyl]-2-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol

Product 1

HCID 86685139[[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]tert-butyl-dimethyl-silaneYield 260.4%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (2S,3R,4S,5S,6R)-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol 15i (1.37 g, 1.69 mmol) in anhydrous tetrahydrofuran (15 mL) was added sodium hydride (0.20 g, 8.45 mmol, 60% dispersion in Mineral oil) at 0° C. The mixture was stirred at 0° C. for 15 min, and then benzyl bromide (1.45 g, 8.45 mmol) and tetrabutylammonium iodide (0.06 g, 0.17 mmol) were added in turn. The mixture was further stirred at room temperature for 20 hours. The reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (20 mL). The aqueous layer was extracted with ethyl acetate (20 mL×3). The combined organic layers were washed with saturated brine (20 mL×3), dried over anhydrous sodium sulfate, filtered. The filtrate was concentrated in vacuo to give the title compound 15j as yellow oil (1.9 g, 100%). This material was not further purified.

Workup

  1. stirringThe mixture was further stirred at room temperature for 20 hours
  2. customThe reaction mixture was quenched with water (10 mL)
  3. extractionextracted with ethyl acetate (20 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (20 mL×3)
  5. washThe combined organic layers were washed with saturated brine (20 mL×3)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-9e6e50e0595348ca8e28b645b1dc9cbc
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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