Sodium Hydroxide → HCID 10178874, compound

HRID 1743648Notes

Reaction equation

HRID 1743648 reaction equation
C[O:2][C:3](=[O:28])[C@H:4]([CH2:13][S:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([O:23][CH2:24][CH:25]=[CH2:26])=[O:22])=[CH:17][C:16]=1[NH2:27])[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].[OH-].[Na+]>CC(OC)(C)C.[Cl-].[Na+]>[C:9]([O:8][C:6]([NH:5][C@H:4]([C:3]([OH:28])=[O:2])[CH2:13][S:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([O:23][CH2:24][CH:25]=[CH2:26])=[O:22])=[CH:17][C:16]=1[NH2:27])=[O:7])([CH3:10])([CH3:11])[CH3:12]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 24243Trisodium PhosphateHCID 58604712HCID 58604712, compound

Product 1

HCID 10178874HCID 10178874, compoundYield 93.9%

Reagents, catalysts & solvents 2

HCID 5234Sodium ChlorideSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

0.769 mg (1.658 mmol) of N-tert-butoxycarbonyl-3-(4-alloxycarbonyl-2-aminophenyl-thio)-L-alanine methyl ester was dissolved in 40 ml TBME and emulsified in 220 ml 0.1M sodium chloride solution; 3 mM sodium phosphate buffer pH 7.5 under vigorous stirring. 1.0 ml Alcalase 2.4 L [a subtilisin Carlsberg from Novo Nordisk] was added and the pH maintained at 7.5 under vigorous stirring by the controlled addition (pH-static) of 1.0N sodium hydroxide solution. After 45.4 h 23.6 ml of 1.0N sodium hydroxide solution was consumed and the conversion degree was >97% (HPLC analysis). The reaction mixture was extracted with 100 ml TBME. After phase separation, the aqueous phase was acidified to pH 2.3 with 32% hydrochloric acid and extracted with 3×250 ml ethyl acetate. In case a stabile emulsion was formed the phase separation was achieved by filtration on Dicalite. The combined ethyl acetate extracts were dried on anhydrous sodium sulfate and evaporated. The residue was dissolved in dichloromethane, evaporated and dried at HV to give 604 mg N-tert-butoxycarbonyl-3-(4-alloxycarbonyl-2-aminophenylthio)-L-alanine as a pale yellow solid (yield: 93.9%, purity: 95%).

Workup

  1. addition1.0 ml Alcalase 2.4 L [a subtilisin Carlsberg from Novo Nordisk] was added
  2. temperaturethe pH maintained at 7.5
  3. customAfter 45.4 h 23.6 ml of 1.0N sodium hydroxide solution was consumed
  4. extractionThe reaction mixture was extracted with 100 ml TBME
  5. customAfter phase separation
  6. extractionextracted with 3×250 ml ethyl acetate
  7. customIn case a stabile emulsion was formed
  8. customthe phase separation
  9. filtrationwas achieved by filtration on Dicalite
  10. dry with materialThe combined ethyl acetate extracts were dried on anhydrous sodium sulfate
  11. customevaporated
  12. dissolutionThe residue was dissolved in dichloromethane
  13. customevaporated
  14. customdried at HV

Sources & evidence

ORD record
ord-6f459793cfc54319892fac37fc62804e
Source dataset
uspto-grants-2006_03
Patent number
US07011960B2

Reaction notes

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