Hydrochloric Acid → Repaglinide

HRID 423216Notes

Reaction equation

HRID 423216 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>CO.O>[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

6

Reactant 3

HCID 313Hydrochloric AcidHCID 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 83.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
62.5 °C

Procedure

Ethyl (S)-2-ethoxy-4-[N-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-amino carbonylmethyl]-benzoate (4.5 g, 0.0093 mol) was dissolved in methanol (45 ml), followed by the addition of sodium hydroxide solution (0.75 g of sodium hydroxide dissolved in 6 ml water). The reaction mixture was heated at 60-65° C. for 3-4 hours. Methanol (80-85%) was removed from the reaction mixture under vacuum. The remaining reaction mixture was diluted with water (45 ml) and pH was adjusted to 6.5-7.0 with 1N HCl. The precipitated solid was stirred for 2-3 hours followed by filtration and washing with water (45 ml). The product was further dried at 50-55° C. under vacuum for 6-8 hours to produce Repaglinide (Yield=83.2%; HPLC Purity: 99.89%).

Workup

  1. customMethanol (80-85%) was removed from the reaction mixture under vacuum
  2. customThe remaining reaction mixture
  3. filtrationfollowed by filtration
  4. washwashing with water (45 ml)
  5. customThe product was further dried at 50-55° C. under vacuum for 6-8 hours

Sources & evidence

ORD record
ord-281ce03874f640e88c967d90904e61fe
Source dataset
uspto-grants-2012_01
Patent number
US08101769B2

Reaction notes

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