Water → Sergliflozin Etabonate

HRID 2222076Notes

Reaction equation

HRID 2222076 reaction equation
[O:1]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)[C@@H:2]1[O:10][C@H:9]([CH2:11][OH:12])[C@@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4].N1C(C)=CC=CC=1C.Cl[C:37]([O:39][CH2:40][CH3:41])=[O:38].O>CC(C)=O.C(OCC)(=O)C>[CH2:40]([O:39][C:37]([O:12][CH2:11][C@H:9]1[O:10][C@@H:2]([O:1][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH2:19][C:20]2[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=2)[C@H:3]([OH:4])[C@@H:5]([OH:6])[C@@H:7]1[OH:8])=[O:38])[CH3:41]

Participants

7

Reactant 4

HCID 962WaterHCID 79372,6-LutidineHCID 10928Ethyl chloroformateHCID 10177526Sergliflozin

Product 1

HCID 9824918Sergliflozin Etabonate

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 2-(4-methoxybenzyl)phenyl β-D-glucopyranoside (220 g) and 2,6-lutidine (136 mL) in acetone (834 mL) was added ethyl chloroformate (84 mL) at about 5 to about 10° C. Thereafter the mixture was stirred at about 10 to about 20° C. for 4 hours. To the reaction mixture were added water and ethyl acetate, and the organic layer was separated. The organic layer was washed successively with a 10% aqueous solution of citric acid, brine, a 10% aqueous solution of sodium bicarbonate and brine, and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and the solvent of the filtrate was removed under reduced pressure. The residue (326 g) was dissolved in ethanol (1039 mL) under heating, and the resulting solution was treated with activated charcoal (11 g). After the mixture was stirred for 5 minutes, insoluble materials were filtered through celite. To the filtrate was added n-hexane (2046 mL) at about 30 to about 40° C. over about 45 minutes, and the resulting mixture was allowed to stand at room temperature for 17 hours. Thereafter, the mixture was stirred under ice-cooling for 2 hours, and the precipitated crystals were collected by filtration to afford crude crystals of 2-(4-methoxybenzyl)phenyl 6-O-ethoxycarbonyl-β-D-glucopyranoside (202 g).

Workup

  1. customthe organic layer was separated
  2. washThe organic layer was washed successively with a 10% aqueous solution of citric acid, brine
  3. dry with materiala 10% aqueous solution of sodium bicarbonate and brine, and dried over anhydrous sodium sulfate
  4. customThe desiccant was removed by filtration
  5. customthe solvent of the filtrate was removed under reduced pressure
  6. dissolutionThe residue (326 g) was dissolved in ethanol (1039 mL)
  7. temperatureunder heating
  8. additionthe resulting solution was treated with activated charcoal (11 g)
  9. stirringAfter the mixture was stirred for 5 minutes
  10. filtrationinsoluble materials were filtered through celite
  11. additionTo the filtrate was added n-hexane (2046 mL) at about 30 to about 40° C. over about 45 minutes
  12. waitto stand at room temperature for 17 hours
  13. stirringThereafter, the mixture was stirred under ice-
  14. temperaturecooling for 2 hours
  15. filtrationthe precipitated crystals were collected by filtration

Sources & evidence

ORD record
ord-af54e4f436df463b9292176894dac002
Source dataset
uspto-grants-2008_05
Patent number
US07371730B2

Reaction notes

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