Sodium Hydroxide → HCID 10222027, compound

HRID 1743644Notes

Reaction equation

HRID 1743644 reaction equation
C[O:2][C:3](=[O:23])[C@H:4]([CH2:13][S:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[NH2:22])[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].[OH-].[Na+]>CC(OC)(C)C>[C:9]([O:8][C:6]([NH:5][C@H:4]([C:3]([OH:23])=[O:2])[CH2:13][S:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[NH2:22])=[O:7])([CH3:12])([CH3:10])[CH3:11]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 58604709HCID 58604709, compound

Product 1

HCID 10222027HCID 10222027, compoundYield 99.9%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

1.65 g (3.99 mmol) of N-tert-butoxycarbonyl-3-(2-amino-4-bromophenylthio)-L-alanine methyl ester (98%) was dissolved in 65 ml TBME and emulsified in 240 ml buffer solution (0.1M sodium chloride; 20 mM sodium phosphate pH 7.5) under vigorous stirring. 0.75 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 33 h, 4.23 ml of 1.0N sodium hydroxide solution was consumed and the conversion degree was >99% (HPLC analysis). The reaction mixture was acidified to pH 2 with 32% hydrochloric acid, filtered over Decalite. After phase separation the aqueous phase was extracted with 3×275 ml ethyl acetate. The combined organic phases were dried on anhydrous sodium sulfate and evaporated. The residue was dissolved in dichloromethane, evaporated and dried at HV to give 1.56 g N-tert-butoxycarbonyl-3-(2-amino-4-bromophenylthio)-L-alanine as a pale yellow solid (yield: 99.8%).

Workup

  1. addition0.75 ml Alcalase 2.4 L [a subtilisin Carlsberg from Novo Nordisk] was added
  2. temperaturethe pH maintained at 7.5
  3. custom4.23 ml of 1.0N sodium hydroxide solution was consumed
  4. filtrationfiltered over Decalite
  5. customAfter phase separation the aqueous phase
  6. extractionwas extracted with 3×275 ml ethyl acetate
  7. dry with materialThe combined organic phases were dried on anhydrous sodium sulfate
  8. customevaporated
  9. dissolutionThe residue was dissolved in dichloromethane
  10. customevaporated
  11. customdried at HV

Sources & evidence

ORD record
ord-4bae51229394436eb062f1d12d2a0fe9
Source dataset
uspto-grants-2006_03
Patent number
US07011960B2

Reaction notes

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