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

HRID 1912983Notes

Reaction equation

HRID 1912983 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][CH2:33][CH2:34][O:35][CH:36]4[CH2:38][CH2:37]4)=[CH:28][CH:27]=3)[CH:19]=2)([O:16][CH3:17])[C@H:13]([OH:39])[C@@H:12]([OH:40])[C@@H:11]1[OH:41])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].[CH2:44](Br)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>CN(C)C=O>[CH2:44]([O:41][C@H:11]1[C@H:12]([O:40][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@@H:13]([O:39][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:27]=[CH:28][C:29]([O:32][CH2:33][CH2:34][O:35][CH:36]4[CH2:38][CH2:37]4)=[CH:30][CH:31]=3)[CH:19]=2)([O:16][CH3:17])[O:15][C@@H:10]1[CH2:9][O:8][Si:1]([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 86685100(2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxymethyl]-2-[4-chloro-3-[[4-[2-(cyclopropoxy)ethoxy]phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol

Product 1

HCID 86685101[[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-[2-(cyclopropoxy)ethoxy]phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]-tert-butyl-dim-ethyl-silaneYield 196.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxymethyl]-2-[4-chloro-3-[[4-[2-(cyclopropoxy)ethoxy]phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol 1b (3.0 g, 4.92 mmol) was dissolved in 50 mL N,N-dimethyl formamide and cooled to 0° C. 60% NaH (984 mg, 24.6 mmol) was added. Then the reaction mixture was warmed to room temperature and stirred for 15 minutes before benzyl bromide (2.95 mL, 24.6 mmol) was added. The mixture was stirred for 16 hours. The reaction mixture was concentrated under reduced pressure after 5 mL methanol were added. The residue was dissolved in 100 mL ethyl acetate and partitioned. The organic extracts were washed with water (50 mL×2) and combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure obtain the crude title compound [[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-[2-(cyclopropoxy)ethoxy]phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]-tert-butyl-dim-ethyl-silane 1c (4.26 g, yellow grease), which was used directly without purification in the next step.

Workup

  1. temperatureThen the reaction mixture was warmed to room temperature
  2. additionwas added
  3. concentrationThe reaction mixture was concentrated under reduced pressure after 5 mL methanol
  4. additionwere added
  5. dissolutionThe residue was dissolved in 100 mL ethyl acetate
  6. custompartitioned
  7. washThe organic extracts were washed with water (50 mL×2)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-460d2985e2da4925941f4f497f3fffd3
Source dataset
uspto-grants-2013_12
Patent number
US08609622B2

Reaction notes

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