Benzyl Bromide → HCID 86685158, compound

HRID 1913061Notes

Reaction equation

HRID 1913061 reaction equation
[C:1]([Si:5]([CH3:40])([CH3:39])[O:6][CH2:7][C@H:8]1[O:13][C@:12]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([CH2:23][C:24]3[S:25][C:26]([C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)=[CH:27][CH:28]=3)[CH:17]=2)([O:14][CH3:15])[C@H:11]([OH:36])[C@@H:10]([OH:37])[C@@H:9]1[OH:38])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:43](Br)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>CN(C=O)C>[CH2:43]([O:38][C@H:9]1[C@H:10]([O:37][CH2:26][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C@@H:11]([O:36][CH2:12][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C@@:12]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([CH2:23][C:24]3[S:25][C:26]([C:29]4[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=4)=[CH:27][CH:28]=3)[CH:17]=2)([O:14][CH3:15])[O:13][C@@H:8]1[CH2:7][O:6][Si:5]([C:1]([CH3:3])([CH3:2])[CH3:4])([CH3:39])[CH3:40])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 86685157HCID 86685157, compound

Product 1

HCID 86685158HCID 86685158, compoundYield 198.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxymethyl]-2-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methyl-phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol 9e (2.0 g, 3.4 mmol) was dissolved in 20 mL DMF and cooled to 0° C., followed by addition of 60% NaH (680 mg, 17 mmol). The reaction mixture was warmed to room temperature and stirred for 30 minutes. Thereafter, benzyl bromide (2.0 mL, 17 mmol) was added before the mixture was stirred for 16 hours. The reaction mixture was concentrated under reduced pressure after 10 mL methanol were added and was partitioned after 30 mL ethyl acetate and 30 mL water were added. The aqueous phase was extracted with ethyl acetate (20 mL×3) and the organic extracts were combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound [[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methyl-phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]tert-butyl-dimethyl-silane 9f (2.9 g, yellow grease), which was used directly in the next step without purification.

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. stirringwas stirred for 16 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure after 10 mL methanol
  4. additionwere added
  5. customwas partitioned after 30 mL ethyl acetate and 30 mL water
  6. additionwere added
  7. extractionThe aqueous phase was extracted with ethyl acetate (20 mL×3)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-b9117c2587674be99c45e635f62d0052
Source dataset
uspto-grants-2013_12
Patent number
US08609622B2

Reaction notes

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