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

HRID 2375197Notes

Reaction equation

HRID 2375197 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-isopropoxyphenyl)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-9b1357ec79bb4c529255cd0d79350afb
Source dataset
uspto-grants-2008_12
Patent number
US07465713B2

Reaction notes

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