Reacción #66025

Ecuación de reacción

{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

Disolventes

THF

MeOH

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGstirred at 0° C. for 30 min
2. 2
   FiltraciónThe 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
   FiltraciónThe reaction mixture was filtered
6. 6
   Otrothe solvent evaporated
7. 7
   workup.DISSOLUTIONthe residue dissolved in H2O (25 mL)
8. 8
   Extracciónthe aqueous layer was extracted with EtOAc (3×30 mL)
9. 9
   SecadoThe combined organic layers were dried over MgSO4
10. 10
    Otroevaporated in vacuo

Procedimiento

{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

Fuente