Methanesulfonic Acid → (3S,4S,5S)-2-(3-((tert-butyldiphenylsilyloxy)methyl)-4-chlorophenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

HRID 2035396Notes

Reaction equation

HRID 2035396 reaction equation
C[Si](C)(C)[O:3][C@H:4]1[C@@H:9]([O:10][Si](C)(C)C)[C@H:8]([O:15][Si](C)(C)C)[CH:7]([CH2:20][O:21][Si](C)(C)C)[O:6][C:5]1=[O:26].Br[C:30]1[CH:31]=[CH:32][C:33]([Cl:55])=[C:34]([CH:54]=1)[CH2:35][O:36][Si:37]([C:50]([CH3:53])([CH3:52])[CH3:51])([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.[Li][C:57](C)(C)C.CS(O)(=O)=O>O1CCCC1.CO>[Si:37]([O:36][CH2:35][C:34]1[CH:54]=[C:30]([C:5]2([O:26][CH3:57])[C@@H:4]([OH:3])[C@@H:9]([OH:10])[C@H:8]([OH:15])[CH:7]([CH2:20][OH:21])[O:6]2)[CH:31]=[CH:32][C:33]=1[Cl:55])([C:50]([CH3:53])([CH3:52])[CH3:51])([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

7

Reactant 4

HCID 6395Methanesulfonic AcidHCID 57516661(5-Bromo-2-chlorobenzyloxy)(tert-butyl)diphenylsilaneHCID 67417628(3S,4S,5R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)tetrahydro-2H-pyran-2-oneHCID 178418306HCID 178418306, compound

Product 1

HCID 67419038(3S,4S,5S)-2-(3-((tert-butyldiphenylsilyloxy)methyl)-4-chlorophenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triolYield 107.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (3S,4S,5R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)tetrahydro-2H-pyran-2-one (3.0 g, 6.5 mmol) and (5-bromo-2-chlorobenzyloxy)(tert-butyl)diphenylsilane (3.7 g, 7.8 mmol) in tetrahydrofuran (105 mL) at −78° C. under nitrogen was added t-BuLi (8.0 mL, 13.7 mmol) dropwise. Reaction was stirred at −78° C. for 5 hours and then a cold (−78° C.) solution of methanesulfonic acid (1.6 mL) in methanol (54 mL) was added to it via cannulation. The cold bath was then removed and the reaction mixture was stirred at room temperature overnight. The reaction solution was quenched with aqueous sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic extract was washed with brine, dried over sodium sulfate and concentrated in vacuo to give (3S,4S,5S)-2-(3-((tert-butyldiphenylsilyloxy)methyl)-4-chlorophenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol (4.0 g, crude, mixture of 2 anomers at 2-position) as a white foam, which was used in the next step without purification.

Workup

  1. customReaction
  2. customThe cold bath was then removed
  3. stirringthe reaction mixture was stirred at room temperature overnight
  4. customThe reaction solution was quenched with aqueous sodium bicarbonate
  5. extractionextracted with ethyl acetate (3×)
  6. extractionThe combined organic extract
  7. washwas washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dd5c838f73c54a7bb9dba0eef31473bd
Source dataset
uspto-grants-2013_11
Patent number
US08575114B2

Reaction notes

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