Sodium Hydroxide → VEL-0230 free acid

HRID 1698115Notes

Reaction equation

HRID 1698115 reaction equation
[CH2:1]([O:5][CH2:6][C@@H:7]([NH:12][C:13]([C@H:15]1[O:17][C@@H:16]1[C:18]([O:20]CC)=[O:19])=[O:14])[CH2:8][CH:9]([CH3:11])[CH3:10])[CH:2]([CH3:4])[CH3:3].[OH-].[Na+]>C(O)C>[CH2:1]([O:5][CH2:6][C@@H:7]([NH:12][C:13]([C@H:15]1[O:17][C@@H:16]1[C:18]([OH:20])=[O:19])=[O:14])[CH2:8][CH:9]([CH3:11])[CH3:10])[CH:2]([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 9948800HCID 9948800, compound

Product 1

HCID 9927318VEL-0230 free acidYield 93.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Crude ethyl (2S,3S)-3-[[(1S)-1-isobutoxymethyl-3-methylbutyl]carbamoyl]oxirane-2-carboxylate (164.54 g) synthesized according to the process described in Patent reference 1 was dissolved in ethanol (520 mL). While the solution was cooled with ice (at a temperature of 10° C. or below), 1 mol/L aqueous sodium hydroxide solution (522 mL) was dropped. After the solution was stirred for 1.5 hours while the temperature was kept, ethanol was removed under reduced pressure. Water (340 mL) was added, and then the mixture was filtered through Celite to remove insoluble materials. The mixture was washed twice with ethyl acetate (300 mL). While the aqueous portion was cooled with ice, 6 mol/L aqueous hydrochloric acid (110 mL) was dropped to adjust the pH value to 1 and then the mixture was extracted twice with ethyl acetate (300 mL). The ethyl acetate portion was washed with water (300 mL) and with aqueous saturated sodium chloride solution (200 mL), and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain (2S,3S)-3-[[(1S)-1-isobutoxymethyl-3-methylbutyl]-carbamoyl]oxirane-2-carboxylic acid (139.61 g, 93.1%) as orange oil. The NMR data were the same as those in Example 6.

Workup

  1. additionwas dropped
  2. customethanol was removed under reduced pressure
  3. additionWater (340 mL) was added
  4. filtrationthe mixture was filtered through Celite
  5. customto remove insoluble materials
  6. washThe mixture was washed twice with ethyl acetate (300 mL)
  7. temperatureWhile the aqueous portion was cooled with ice, 6 mol/L aqueous hydrochloric acid (110 mL)
  8. additionwas dropped
  9. extractionthe mixture was extracted twice with ethyl acetate (300 mL)
  10. washThe ethyl acetate portion was washed with water (300 mL) and with aqueous saturated sodium chloride solution (200 mL)
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-3ad8f7922a9643a480122b1447e3618e
Source dataset
uspto-grants-2012_04
Patent number
US08163942B2

Reaction notes

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