Citric Acid → Sergliflozin Etabonate

HRID 2222075Notes

Reaction equation

HRID 2222075 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].Cl[C:29]([O:31][CH2:32][CH3:33])=[O:30].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CC1C=C(C)C=C(C)N=1>[CH2:32]([O:31][C:29]([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:30])[CH3:33]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 10928Ethyl chloroformateHCID 10177526Sergliflozin

Product 1

HCID 9824918Sergliflozin Etabonate

Reagents, catalysts & solvents 1

HCID 79532,4,6-TrimethylpyridineSolvent

Procedure

To a solution of 2-(4-methoxybenzyl)phenyl β-D-glucopyranoside (0.075 g) in 2,4,6-trimethylpyridine (2 mL) was added ethyl chloroformate (0.04 mL) at room temperature. After the mixture was stirred at room temperature for 16 hours, a saturated aqueous solution of citric acid was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by preparative thin layer chromatography on silica gel (eluent:dichloromethane/methanol=10/1) to give an amorphous form of 2-(4-methoxybenzyl)phenyl 6-O-ethoxycarbonyl-β-D-glucopyranoside (0.032 g). As a result of X-ray powder diffraction analysis, the amorphous substance shows no distinct peak. 1H-NMR (CD3OD) δ ppm: 1.23 (3H, t, J=7.1 Hz), 3.30-3.65 (4H, m), 3.74 (3H, s), 3.93 (1H, d, J=15.1 Hz), 4.02 (1H, d, J=15.1 Hz), 4.05-4.20 (2H, m), 4.29 (1H, dd, J=6.4,11.7 Hz), 4.45 (1H, dd, J=2.2, 11.7 Hz), 4.89 (1H, d, J=7.4 Hz), 6.75-6.85(2H, m), 6.85-7.05 (2H, m), 7.05-7.2 (4H, m)

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was removed under reduced pressure
  5. customThe residue was purified by preparative thin layer chromatography on silica gel (eluent:dichloromethane/methanol=10/1)

Sources & evidence

ORD record
ord-53a6749174104a6daede83aa128d0363
Source dataset
uspto-grants-2008_05
Patent number
US07371730B2

Reaction notes

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