Sodium Hydroxide → Repaglinide

HRID 858367Notes

Reaction equation

HRID 858367 reaction equation
[CH2:1]([O:3][C:4]1[CH:14]=[C:13]([CH2:15][C:16]([NH:18][C@H:19]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[N:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[CH2:20][CH:21]([CH3:23])[CH3:22])=[O:17])[CH:12]=[CH:11][C:5]=1[C:6]([O:8]CC)=[O:7])[CH3:2].[OH-].[Na+]>Cl>[CH3:2][CH2:1][O:3][C:4]1[CH:14]=[C:13]([CH2:15][C:16]([NH:18][C@H:19]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[N:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[CH2:20][CH:21]([CH3:23])[CH3:22])=[O:17])[CH:12]=[CH:11][C:5]=1[C:6]([OH:8])=[O:7]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 106484192-Ethoxy-4-(3-((S)-3-methy-1-(2-piperidin-1-yl-phenyl)-butylamino)-2-oxo-propyl)-benzoic acid ethyl ester

Product 1

HCID 65981RepaglinideYield 94.5%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
60 °C

Procedure

A solution of ethyl (S)-2-ethoxy-4-[N-{1-(2-piperidinophenyl)-3-methyl-1-butyl}-aminocarbonylmethyl]benzoate (20 g, 41.6 mmol) in denatured spirit (200 ml) was stirred at 60–65° C. and 1N sodium hydroxide solution (62 ml) was added. After two hours of stirring at 60° C., the reaction mixture was cooled to 35° C. and pH was adjusted to about 5.0 using 1N hydrochloric acid (about 70 ml). The solution was stirred for 30 minutes at 35–40° C., cooled to 0° C. and stirred at 0 to 5° C. for one hour to get a crystalline product. The crystals were separated by filtration and washed with water. The product was dried at 60–65° C. under vacuum to get repaglinide (17.8 g, Yield: 94%, Assay 99.5% by HPLC).

Workup

  1. temperaturethe reaction mixture was cooled to 35° C.
  2. stirringThe solution was stirred for 30 minutes at 35–40° C.
  3. temperaturecooled to 0° C.
  4. stirringstirred at 0 to 5° C. for one hour
  5. customto get a crystalline product
  6. customThe crystals were separated by filtration
  7. washwashed with water
  8. customThe product was dried at 60–65° C. under vacuum

Sources & evidence

ORD record
ord-464289acb3e04613bba0340d6ad8a007
Source dataset
uspto-grants-2006_12
Patent number
US07148355B2

Reaction notes

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