Methanesulfonic Acid → Methyl 1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-D-glucopyranoside

HRID 2174326Notes

Reaction equation

HRID 2174326 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=2)[CH:3]=1.[Li][CH2:20]CCC.C[Si](C)(C)[O:26][C@@H:27]1[C@@H:32]([O:33][Si](C)(C)C)[C@H:31]([O:38][Si](C)(C)C)[C@@H:30]([CH2:43][O:44][Si](C)(C)C)[O:29][C:28]1=[O:49].CS(O)(=O)=O>C1(C)C=CC=CC=1.C1COCC1.C1(C)C=CC=CC=1.CO>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C:28]2([O:49][CH3:20])[C@H:27]([OH:26])[C@@H:32]([OH:33])[C@H:31]([OH:38])[C@@H:30]([CH2:43][OH:44])[O:29]2)=[CH:3][C:4]=1[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=1

Participants

8

Reactant 4

HCID 6395Methanesulfonic AcidHCID 99964494-Bromo-1-chloro-2-(4-ethoxy-benzyl)-benzeneHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 178418339Butyllithium

Product 1

HCID 10252611Methyl 1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-D-glucopyranoside

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Conditions

Temperature
-65 °C

Procedure

To 4-bromo-1-chloro-2-(4-ethoxybenzyl)benzene (10 g, 0.031 mol) in anhydrous toluene/THF (78 mL, v/v=2:1) was added dropwise n-BuLi (2.5 M in hexane, 13.5 mL) at −65° C. and stirred for 30 minutes at −65° C. The mixture was transferred to a solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)tetrahydro-2H-pyran-2-one (15.7 g, 0.034 mol) in toluene (78 mL) at −65° C. The mixture was stirred at −65° C. for 2 hours until starting material was consumed. The reaction was quenched with methanesulfonic acid (4.18 mL, 0.065 mol) in methanol (70 mL), and the mixture was allowed to warm to RT and stirred overnight. The reaction was quenched with saturated sodium bicarbonate, the organic phase was separated, and the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with saturated bicarbonate, then with water, then with brine, and were dried over sodium sulfate. After removal of the volatiles, the residue was slurried in toluene/hexane (120 mL, 1:5), filtered, and dried under vacuum to give compound 4 as a white solid (12.5 g). The crude product was used in the next step without further purification.

Workup

  1. stirringThe mixture was stirred at −65° C. for 2 hours
  2. customwas consumed
  3. temperatureto warm to RT
  4. stirringstirred overnight
  5. customThe reaction was quenched with saturated sodium bicarbonate
  6. customthe organic phase was separated
  7. extractionthe aqueous phase was extracted with ethyl acetate
  8. washThe combined organic phases were washed with saturated bicarbonate
  9. dry with materialwith water, then with brine, and were dried over sodium sulfate
  10. customAfter removal of the volatiles
  11. filtrationfiltered
  12. customdried under vacuum

Sources & evidence

ORD record
ord-3d8d05155072449690a515ccbd7e301e
Source dataset
uspto-grants-2015_06
Patent number
US09061060B2

Reaction notes

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