Methanesulfonic Acid → HCID 71110534, compound

HRID 576417Notes

Reaction equation

HRID 576417 reaction equation
[Cl:1][C:2]1[C:7]2[CH2:8][CH:9]([CH3:11])[O:10][C:6]=2[C:5]([C:12]2(O)[C@H:17]([O:18][Si](C)(C)C)[C@@H:16]([O:23][Si](C)(C)C)[C@H:15]([O:28][Si](C)(C)C)[C@@H:14]([CH2:33][O:34][Si](C)(C)C)[O:13]2)=[CH:4][C:3]=1[CH2:40][C:41]1[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH3:49])=[CH:43][CH:42]=1.CS(O)(=O)=O.C([O-])(O)=O.[Na+].C([SiH](CC)CC)C.B(F)(F)F.CCOCC>C1COCC1.C(Cl)Cl.CC#N.O>[Cl:1][C:2]1[C:7]2[CH2:8][CH:9]([CH3:11])[O:10][C:6]=2[C:5]([C@H:12]2[C@H:17]([OH:18])[C@@H:16]([OH:23])[C@H:15]([OH:28])[C@@H:14]([CH2:33][OH:34])[O:13]2)=[CH:4][C:3]=1[CH2:40][C:41]1[CH:42]=[CH:43][C:44]([O:47][CH2:48][CH3:49])=[CH:45][CH:46]=1

Participants

9

Reactant 5

HCID 6395Methanesulfonic AcidHCID 8000Boron trifluoride etherateHCID 12052TriethylsilaneHCID 516892Sodium Bicarbonate2×HCID 131732862HCID 131732862, compound

Product 1

HCID 71110534HCID 71110534, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 21877088Acetonitrile methylene chlorideSolvent

Conditions

Temperature
-30 °C

Procedure

To a solution of the crude alcohol (4.46 g, 5.79 mmol) in THF (50 mL) were added CH3SO3H (0.6 N in MeOH, 18 mL, 10.4 mmol) at −78° C. The mixture was allowed to slowly warm to −30° C. To a mixture was added aq. saturated NaHCO3 solution (50 mL) to quench the reaction. After dilution with water, the mixture was stirred at room temperature for 30 min and extracted with EtOAc (100 mL×2). The organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude (3R,4S,5S,6R)-2-(4-chloro-5-(4-ethoxybenzyl)-2-methyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol (2.52 g) was carried on to the next step without further purification. To a solution of the triol compound (2.52 g) in CH2Cl2/CH3CN (25 mL/25 mL) were added triethylsilane (1.7 mL, 10.2 mmol) and boron trifluoride diethyl etherate (1.3 mL, 10.2 mmol) at −60° C. The mixture was allowed to slowly warm to −10° C. To a mixture was added aq. saturated NaHCO3 solution (20 mL) to quench the reaction. The reaction mixture was stirred at r.t. and evaporated in vacuo to remove CH2Cl2 and CH3CN. The mixture was extracted with EtOAc (100 mL×2). The combined organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified using reverse phase preparative HPLC to provide the title compound E011 (81 mg, 2.8% (3-steps)).

Workup

  1. customto quench
  2. customthe reaction
  3. extractionextracted with EtOAc (100 mL×2)
  4. dry with materialThe organic layer was dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude (3R,4S,5S,6R)-2-(4-chloro-5-(4-ethoxybenzyl)-2-methyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol (2.52 g) was carried on to the next step without further purification
  8. temperatureto slowly warm to −10° C
  9. customto quench
  10. customthe reaction
  11. customevaporated in vacuo
  12. customto remove CH2Cl2 and CH3CN
  13. extractionThe mixture was extracted with EtOAc (100 mL×2)
  14. dry with materialThe combined organic layer was dried over MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customThe residue was purified

Sources & evidence

ORD record
ord-34aeef58a3df4492ad690bdd3f1f024b
Source dataset
uspto-grants-2015_05
Patent number
US09034921B2

Reaction notes

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