Tetrahydrofuran → N-{4-[3-(4-Fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-malonamic acid methyl ester

To a solution of 4-(4-amino-2,6-dimethyl-phenoxy)-2-(4-fluoro-benzenesulfonyl)-phenol (5.53 g, 14.3 mmol) in dry THF (30 mL) was added methyl malonyl chloride (1.68 mL, 15.7 mmol). The solution was stirred 2 h at RT then concentrated to a pink solid. The solid was dissolved in a minimal amount of CH2Cl2, passed through silica gel and eluted with 2% methanol in CH2Cl2 (750 mL). The solution was concentrated to a pink solid, and the solid was dissolved in EtOAc (30 ml) and cyclohexane (200 mL) was added gradually to give an oily solid, which became more crystalline on stirring at RT. The suspension was stirred 24 h at RT, then filtered. The white solid was washed with cyclohexane (3×20 mL) and petroleum ether (20 mL) and dried to give the title compound of Step E (4.88 g). MS (APCl+) Calc.:487.1, Found: 488.3 (M+1).

1. concentrationthen concentrated to a pink solid
2. dissolutionThe solid was dissolved in a minimal amount of CH2Cl2
3. washeluted with 2% methanol in CH2Cl2 (750 mL)
4. concentrationThe solution was concentrated to a pink solid
5. dissolutionthe solid was dissolved in EtOAc (30 ml)
6. additioncyclohexane (200 mL) was added gradually
7. customto give an oily solid, which
8. stirringon stirring at RT
9. stirringThe suspension was stirred 24 h at RT
10. filtrationfiltered
11. washThe white solid was washed with cyclohexane (3×20 mL) and petroleum ether (20 mL)
12. customdried

ORD record

ord-2fb4b44c456c41f9ba86841ecd1746c7

Source dataset

uspto-grants-2003_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06664291B2