Reaction #66025

Reaction equation

{Carboxymethyl-[4-(4-bromo-phenoxy)-benzenesulphonyl]-amino}-acetic acid

{[4-(4-Fluoro-phenoxy)-benzenesulphonyl]-tert-butoxycarbonylmethyl-amino}-aceticacid tert-butyl ester

NMM

NH2OH

HCl

KOH

→

product

{[4-(4-Fluoro-phenoxy)-benzenesulphonyl]-hydroxycarbamoylmethyl-amino}-acetic acid

Solvents

THF

MeOH

Conditions

Workup

1. 1
   workup.STIRRINGstirred at 0° C. for 30 min
2. 2
   FiltrationThe solids were filtered off
3. 3
   workup.ADDITIONthe THF solution was added dropwise to the methanol filtrate
4. 4
   workup.STIRRINGstirred for 2 h at 0° C
5. 5
   FiltrationThe reaction mixture was filtered
6. 6
   Otherthe solvent evaporated
7. 7
   workup.DISSOLUTIONthe residue dissolved in H2O (25 mL)
8. 8
   Extractionthe aqueous layer was extracted with EtOAc (3×30 mL)
9. 9
   DryingThe combined organic layers were dried over MgSO4
10. 10
    Otherevaporated in vacuo

Procedure

{Carboxymethyl-[4-(4-bromo-phenoxy)-benzenesulphonyl]-amino}-acetic acid (4b) (500 mg, 1.30 mmol) was dissolved in dry THF (10 mL). ECF (100 μL, 1.12 mmol), and NMM (120 μL, 1.12 mmol) were added and stirred for 40 min at 0° C. NH2OH×HCl (90 mg, 1.30 mmol) and KOH (73 mg, 1.30 mmol) were dissolved in dry MeOH (10 mL) and stirred at 0° C. for 30 min. The solids were filtered off, and the THF solution was added dropwise to the methanol filtrate and stirred for 2 h at 0° C. The reaction mixture was filtered, the solvent evaporated, and the residue dissolved in H2O (25 mL). After adjusting the pH to 1-2, the aqueous layer was extracted with EtOAc (3×30 mL). The combined organic layers were dried over MgSO4, evaporated in vacuo, and co-evaporated with EtOAc (3×3 mL) to yield the pure product as light-pink solid. Yield: 267 mg, 0.67 mmol, 52%. 1H-NMR (DMSO-d6): δ 7.91 (dd, 2H, 3JHH=9.0 Hz, 4JHF=5.1 Hz, ArH), 7.42 (t, 2H, 3JHH=9.0 Hz, 3JHF=9.0 Hz, ArH), 4.07 (s, 4H, 2×CH2CO2H). ESI-MS calcd for C16H15FN2O7S 398.06 [M-H]−, obsd 399.10

Source