Methanesulfonic Acid → (3R,4S,5S,6R)-2-(4-Chloro-3-(4-ethoxybenzyl)-5-methoxyphenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

HRID 2206713Notes

Reaction equation

HRID 2206713 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:19][CH3:20])[C:5]([Cl:18])=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[CH:11][CH:10]=2)[CH:7]=1.[CH2:21]([Li])CCC.[CH2:26]([OH:37])[C@H:27]1[O:33][C:31](=[O:32])[C@H:30]([OH:34])[C@@H:29]([OH:35])[C@@H:28]1[OH:36].CS(O)(=O)=O.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C1COCC1.C1(C)C=CC=CC=1.O>[Cl:18][C:5]1[C:4]([O:19][CH3:20])=[CH:3][C:2]([C:31]2([O:32][CH3:21])[C@H:30]([OH:34])[C@@H:29]([OH:35])[C@H:28]([OH:36])[C@@H:27]([CH2:26][OH:37])[O:33]2)=[CH:7][C:6]=1[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[CH:11][CH:10]=1

Participants

9

Reactant 5

HCID 6395Methanesulfonic AcidHCID 7027delta-GluconolactoneHCID 516892Sodium BicarbonateHCID 710769175-Bromo-2-chloro-1-(4-ethoxybenzyl)-3-methoxybenzeneHCID 178418339Butyllithium

Product 1

HCID 71076921(3R,4S,5S,6R)-2-(4-Chloro-3-(4-ethoxybenzyl)-5-methoxyphenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of bromide 74 (5.74 g, 16.14 mmol) in toluene/THF (72 mL/36 mL) at −78° C. under an atmosphere of nitrogen was added dropwise n-butyllithium (2.5 M in hexane, 7.8 mL, 19.36 mmol), and the mixture was stirred for 40 min at the same temperature. Then a solution of TMS-protected gluconolactone 74-1 (9.04 g, 19.36 mmol) in toluene (30 mL) was added dropwise, and the mixture was stirred for 1 hour at the same temperature. To a solution of crude alcohol 74-2 were added CH3SO3H (0.6 N in MeOH, 53.8 mL, 32.28 mmol) at −78° C. The mixture was allowed to slowly warm to −40° 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). The organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The (3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)-5-methoxyphenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol 74-3 (6.6 g) was carried on to the next step without further purification.

Workup

  1. additionwas added dropwise
  2. stirringthe mixture was stirred for 1 hour at the same temperature
  3. customto quench
  4. customthe reaction
  5. extractionextracted with EtOAc (100 mL)
  6. dry with materialThe organic layer was dried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe (3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)-5-methoxyphenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol 74-3 (6.6 g) was carried on to the next step without further purification

Sources & evidence

ORD record
ord-86d7cce0339c495d8e52eba66a7c8242
Source dataset
uspto-grants-2016_06
Patent number
US09371303B2

Reaction notes

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