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

HRID 746405Notes

Reaction equation

HRID 746405 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-3b91581ef7c84839b701916717ad632b
Source dataset
uspto-grants-2008_07
Patent number
US07393838B2

Reaction notes

Loading…