Water → 4-[(4-isopropoxyphenyl)methyl]-1-isopropyl-5-methyl-3-(6-O-propionyl-beta-D-glucopyranosyloxy)pyrazole

HRID 1668330Notes

Reaction equation

HRID 1668330 reaction equation
[C@@H:1]1([O:12][C:13]2[C:17]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]([CH3:28])[CH3:27])=[CH:21][CH:20]=3)=[C:16]([CH3:29])[N:15]([CH:30]([CH3:32])[CH3:31])[N:14]=2)[O:9][C@H:8]([CH2:10][OH:11])[C@@H:6]([OH:7])[C@H:4]([OH:5])[C@H:2]1[OH:3].[C:33](Cl)(=[O:36])[CH2:34][CH3:35].O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.O>CC1C=C(C)C=C(C)N=1>[CH:26]([O:25][C:22]1[CH:23]=[CH:24][C:19]([CH2:18][C:17]2[C:13]([O:12][C@@H:1]3[O:9][C@H:8]([CH2:10][O:11][C:33](=[O:36])[CH2:34][CH3:35])[C@@H:6]([OH:7])[C@H:4]([OH:5])[C@H:2]3[OH:3])=[N:14][N:15]([CH:30]([CH3:32])[CH3:31])[C:16]=2[CH3:29])=[CH:20][CH:21]=1)([CH3:27])[CH3:28]

Participants

6

Reactant 4

HCID 962WaterHCID 222302-Hydroxy-1,2,3-propanetricarboxylic acid hydrate (1:1)HCID 62324Propionyl chlorideHCID 9846588Remogliflozin

Product 1

HCID 673357484-[(4-isopropoxyphenyl)methyl]-1-isopropyl-5-methyl-3-(6-O-propionyl-beta-D-glucopyranosyloxy)pyrazoleYield 65.8%

Reagents, catalysts & solvents 1

HCID 79532,4,6-TrimethylpyridineSolvent

Procedure

To a solution of 3-(β-D-glucopyranosyloxy)-4-[(4-iso-propoxyphenyl)methyl]-1-isopropyl-5-methylpyrazole (0.10 g) in 2,4,6-trimethylpyridine (1 mL) was added propionyl chloride (0.072 g) at 0° C., and the mixture was stirred for hours. To the reaction mixture were added citric acid monohydrate (3.3 g) and water, and the resulting mixture was purified by ODS solid phase extraction (washing solvent: distilled water, eluent: methanol). Further purification by column chromatography on silica gel (eluent: dichloromethane/methanol=10/1) afforded 4-[(4-isopropoxyphenyl)methyl]-1-isopropyl-5-methyl-3-(6-O-propionyl-β-D-glucopyranosyloxy)pyrazole (0.074 g)

Workup

  1. distillationthe resulting mixture was purified by ODS solid phase extraction (washing solvent: distilled water, eluent: methanol)
  2. customFurther purification by column chromatography on silica gel (eluent: dichloromethane/methanol=10/1)

Sources & evidence

ORD record
ord-88d369e858614b0e9c70fbe8de34d9ba
Source dataset
uspto-grants-2011_08
Patent number
US07989424B2

Reaction notes

Loading…