Sodium Hydroxide → HCID 11325740, compound

HRID 1743652Notes

Reaction equation

HRID 1743652 reaction equation
C[O:2][C:3](=[O:25])[C@H:4]([CH2:13][S:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([OH:23])=[O:22])=[CH:17][C:16]=1[NH2:24])[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:25])=[O:2])[CH2:13][S:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([OH:23])=[O:22])=[CH:17][C:16]=1[NH2:24])=[O:7])([CH3:12])([CH3:10])[CH3:11]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 11428666HCID 11428666, compound

Product 1

HCID 11325740HCID 11325740, compoundYield 93.4%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

200 mg (0.540 mmol) of N-tert-butoxycarbonyl-3-(4-carboxy-2-aminophenylthio)-L-alanine methyl ester was added to a system consisting of 5 ml TBME and 20 ml buffer solution (0.1M sodium chloride; 3 mM sodium phosphate pH 7.0) under vigorous stirring. 100 μl of Alcalase 2.5 L [a subtilisin Carlsberg from Novo Nordisk] was added and the pH maintained at 7.0 under vigorous stirring by the controlled addition (pH-static) of 0.1N sodium hydroxide solution. After a consumption 5.847 ml of titrating agent (108% of theory; after 1.5 h) the reaction mixture was washed twice with 25 ml TBME, acidified to pH 2.5 with 25% HCl and extracted with 3×25 ml ethyl acetate. The combined organic phases were dried over sodium sulfate, the solvent evaporated and the residue dried on a HV to give 187 mg (0.479 mmol) N-tert-butoxycarbonyl-3-(2-amino-4-carboxyphenylthio)-L-alanine as yellow crystals (yield: 93.4%). Analytical data: HPLC-purity: 96.4%% (area). 1H-NMR (DMSO, 400 MHz) 1.378 (s, 9H, OC(CH3)); 2.982 (dd, 1H, SCH2, J=13.2 Hz, J=9.6 Hz); 3.150 (dd, 1H, SCH2, J=13.2 Hz, J=4.4 Hz); 3.950 (m, 1H, COCHNH); 5.542 (m, 2H, —NH2); 7.067 (dd, 1H, CONHCH, J=8.0 Hz, J=1.6 Hz); 7.201 (d, 1H, arom. SCCH, J=8.0 Hz); 7.298 (d, 1H, arom. SCCHCH, J=8.0 Hz); 7.323 (d, 1H, arom. CHCNH2, J=1.6 Hz); 12.73 (bs, 2H, 2 —COOH). IR: 3445 and 3347 cm−1 (—NH, —NH2); 2977 and 2930 cm−1 broad (—COOH); 1720 and 1692 cm−1 (COOH —C═O, carbamate —C═O); 1608 cm−1 (—COO−); 1509 cm−1 (amide —CO—NH); 1486 cm−1 (aromate); 1247 and 1163 cm−1 (COOH). ISN-MS: m/z=355.1 [M−H+]. OR [α]D=+13.00° (EtOH; c=1.0).

Workup

  1. addition100 μl of Alcalase 2.5 L [a subtilisin Carlsberg from Novo Nordisk] was added
  2. temperaturethe pH maintained at 7.0
  3. customAfter a consumption 5.847 ml of titrating agent (108% of theory; after 1.5 h) the reaction mixture
  4. washwas washed twice with 25 ml TBME
  5. extractionextracted with 3×25 ml ethyl acetate
  6. dry with materialThe combined organic phases were dried over sodium sulfate
  7. customthe solvent evaporated
  8. customthe residue dried on a HV

Sources & evidence

ORD record
ord-5efb4b7d14ee4aa390331232bddcaa8c
Source dataset
uspto-grants-2006_03
Patent number
US07011960B2

Reaction notes

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