Hydrochloric Acid → HCID 22958558, compound

HRID 2304318Notes

Reaction equation

HRID 2304318 reaction equation
[H-].[Na+].[NH2:3][C@@H:4]([C:9]([OH:11])=[O:10])[C:5]([SH:8])([CH3:7])[CH3:6].[C:12]([O:16][C:17](=[O:20])[CH2:18]Br)([CH3:15])([CH3:14])[CH3:13].Cl>C(O)C>[C:12]([O:16][C:17]([CH2:18][S:8][C:5]([CH3:7])([CH3:6])[C@H:4]([NH:3][C:17]([O:16][CH2:12][CH3:13])=[O:20])[C:9]([OH:11])=[O:10])=[O:20])([CH3:15])([CH3:14])[CH3:13]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 5852PenicillamineHCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetate

Product 1

HCID 22958558HCID 22958558, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
5 °C

Procedure

NaH (0.81 g; 35.2 mmol) was added in portions to 40 mL ethanol while cooling. Subsequently D-penicillamine (2.50 g) was added. The mixture kept stirring for 5 minutes at 5° C., after which bromoacetic acid tert.-butyl ester (2.55 mL) was added. The mixture was allowed to stir 16 h at ambient temperature and subsequently hydrolyzed with 2 N HCl. The solvents were distilled off, the residue was redissolved in 50 mL of water and 50 mL of dioxane and pH 9.5 was adjusted by adding aqueous NaOH. Ethyl chloroformate (2.1 mL) was slowly added at 5° C. while maintaining pH 9.5 by addition of the appropriate amount of aqueous NaOH. Stirring was continued for 6 h at room temperature. Aqueous NaOH was added (pH 10) and the dioxane removed in vacuo followed by extraction of the remaining aqueous solution with ethyl acetate. KHSO4 was added and the acidified aqueous solution extracted with ethyl acetate several times. Evaporation of the solvent in vacuo gave a colorless oil, which was purified by HPLC (RP-18; pH 2.3; H2O/CH3OH 3/7) to give 0.86 g (15%) of the title compound as a colorless oil. (+)-APCI-MS: 358 (MNa+).

Workup

  1. temperaturewhile cooling
  2. distillationThe solvents were distilled off
  3. dissolutionthe residue was redissolved in 50 mL of water
  4. additionby adding aqueous NaOH
  5. additionEthyl chloroformate (2.1 mL) was slowly added at 5° C.
  6. temperaturewhile maintaining pH 9.5
  7. additionby addition of the appropriate amount of aqueous NaOH
  8. stirringStirring
  9. waitwas continued for 6 h at room temperature
  10. additionAqueous NaOH was added (pH 10)
  11. customthe dioxane removed in vacuo
  12. extractionfollowed by extraction of the remaining aqueous solution with ethyl acetate
  13. additionKHSO4 was added
  14. extractionthe acidified aqueous solution extracted with ethyl acetate several times
  15. customEvaporation of the solvent in vacuo
  16. customgave a colorless oil, which
  17. customwas purified by HPLC (RP-18; pH 2.3; H2O/CH3OH 3/7)

Sources & evidence

ORD record
ord-ff4650d439c04edf97151ac56e3d5eb1
Source dataset
uspto-grants-2002_08
Patent number
US06432955B1

Reaction notes

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