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 1913039Notes

Reaction equation

HRID 1913039 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>CN(C=O)C>[CH2:42]([O:39][C@H:11]1[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][C@@H:10]1[CH2:9][O:8][Si:1]([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

5

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 199.8%

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-(trifluoromethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol 6j (1.60 g, 2.69 mmol) was dissolved in 15 mL DMF and cooled to 0° C., followed by addition of 60% NaH (0.54 g, 13.5 mmol). Then the reaction mixture was warmed and stirred for 15 minutes at room temperature before benzyl bromide (1.6 mL, 13.5 mmol) was added. After stirring for 16 hours, the reaction mixture was concentrated under reduced pressure after 5 mL methanol were added. Then the resulting residue was dissolved in ethyl acetate (100 mL) and washed with water (50 mL×2). The organic extract was 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-(trifluoromethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]tert-butyl-dimethyl-silane 6k (2.32 g, yellow grease), which was used directly in the next step without purification.

Workup

  1. temperatureThen the reaction mixture was warmed
  2. additionwas added
  3. concentrationthe reaction mixture was concentrated under reduced pressure after 5 mL methanol
  4. additionwere added
  5. dissolutionThen the resulting residue was dissolved in ethyl acetate (100 mL)
  6. washwashed with water (50 mL×2)
  7. extractionThe organic extract
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-2a67e973d8d24c878fb974fd1a87a23f
Source dataset
uspto-grants-2013_12
Patent number
US08609622B2

Reaction notes

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