Methanol → [[(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 1913050Notes

Reaction equation

HRID 1913050 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][C:34]([F:37])([F:36])[F:35])=[CH:28][CH:27]=3)[CH:19]=2)([O:16][CH3:17])[C@H:13]([OH:38])[C@@H:12]([OH:39])[C@@H:11]1O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].[CH2:43](Br)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.[CH3:51][OH:52]>CN(C=O)C.O>[CH2:51]([O:52][C@H:11]1[C@H:12]([O:39][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C@@H:13]([O:38][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][C:34]([F:35])([F:36])[F:37])=[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]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3])[C:29]1[CH:28]=[CH:27][CH:26]=[CH:31][CH:30]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 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-silane

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxymethyl]-2-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol 7f (2.90 g, 4.78 mmol) was dissolved in 70 mL DMF and cooled to 0° C., followed by addition of 60% NaH (955 mg, 23.9 mmol). The reaction mixture was warmed and stirred for 1 hour at room temperature before benzyl bromide (3.0 mL, 23.9 mmol) was added. After stirring for 3 hours, 5 mL methanol and 10 mL water were added. The reaction mixture was partitioned after 100 mL water and 30 mL saturated sodium chloride solution were added. The aqueous phase was extracted with ethyl acetate (50 mL×3) and the organic extract was washed with saturated sodium chloride solution (30 mL) and 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-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phen yl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]tert-butyl-dimethyl-silane 7g (4.60 g, pale yellow liquid), which was used directly in the next step without purification.

Workup

  1. temperatureThe reaction mixture was warmed
  2. additionwas added
  3. customThe reaction mixture was partitioned after 100 mL water and 30 mL saturated sodium chloride solution
  4. additionwere added
  5. extractionThe aqueous phase was extracted with ethyl acetate (50 mL×3)
  6. extractionthe organic extract
  7. washwas washed with saturated sodium chloride solution (30 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-6e492f7d52884e50a880a378b84de9b9
Source dataset
uspto-grants-2013_12
Patent number
US08609622B2

Reaction notes

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