Water → 3-(6-O-ethoxy-carbonyl-beta-D-glucopyranosyloxy)-4-[(4-isopropoxyphenyl)-methyl]-1-isopropyl-5-methylpyrazole

HRID 33132Notes

Reaction equation

HRID 33132 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].ClC([O:36][CH2:37][CH3:38])=O.O.C(O)(=O)C[C:42](CC(O)=O)(C(O)=O)[OH:43].O>CC1C=C(C)C=C(C)N=1>[CH2:37]([O:36][O:11][C:10](=[C:42]=[O:43])[C@H:8]1[O:9][C@@H:1]([O:12][C:13]2[C:17]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]([CH3:27])[CH3:28])=[CH:21][CH:20]=3)=[C:16]([CH3:29])[N:15]([CH:30]([CH3:32])[CH3:31])[N:14]=2)[C@H:2]([OH:3])[C@@H:4]([OH:5])[C@@H:6]1[OH:7])[CH3:38]

Participants

6

Reactant 4

HCID 962WaterHCID 10928Ethyl chloroformateHCID 222302-Hydroxy-1,2,3-propanetricarboxylic acid hydrate (1:1)HCID 9846588Remogliflozin

Product 1

HCID 866027893-(6-O-ethoxy-carbonyl-beta-D-glucopyranosyloxy)-4-[(4-isopropoxyphenyl)-methyl]-1-isopropyl-5-methylpyrazoleYield 72.7%

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 ethyl chloroformate (0.072 g), and the mixture was stirred at room temperature overnight. 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) and recrystallization (recrystallization solvent: ethyl acetate/hexane=1/3) afforded 3-(6-O-ethoxy-carbonyl-β-D-glucopyranosyloxy)-4-[(4-isopropoxyphenyl)methyl]-1-isopropyl-5-methylpyrazole (0.084 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
  3. customon silica gel (eluent: dichloromethane/methanol=10/1) and recrystallization (recrystallization solvent: ethyl acetate/hexane=1/3)

Sources & evidence

ORD record
ord-4f889f2c3e8f4a7fbe3c8ca1366ea54d
Source dataset
uspto-grants-2008_09
Patent number
US07429568B2

Reaction notes

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