Ethyl Acetate → Ethyl 6-chloro-5-hydroxynicotinate

Temperatur

80 °C

To a stirred mixture of ethyl 5-hydroxynicotinate (20 g, 0.119 mol, in DMF (200.0 mL) was added NCS (19.18 g, 0.143 mol, Aldrich). The reaction mixture was stirred for 2 h at 80° C. After completion of the reaction (monitored by TLC, 30% EtOAc in hexane), the reaction mixture was quenched with sat'd NaHCO3 solution (50 mL) and extracted with EtOAc (500 mL×3). The combined organic layers were dried over anhydrous sodium sulfate, and purified by column chromatography, silica gel (100-200 mesh), using 10-15% EtOAc in petroleum ether as the eluent to give the title compound as a solid. 1H NMR (400 MHz, CDCl3) δ: 8.61 (d, J=2.1 Hz, 1H), 7.92 (d, J=1.8 Hz, 1H), 5.94 (br. s., 1H), 4.53 (q, J=6.9 Hz, 2H), 1.43 (t, J=7.2 Hz, 3H). MS (ESI, positive ion) m/z: 202.1 (M+H).

1. customthe reaction mixture was quenched with sat'd NaHCO3 solution (50 mL)
2. extractionextracted with EtOAc (500 mL×3)
3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
4. custompurified by column chromatography, silica gel (100-200 mesh)

ORD-Eintrag

ord-9187690f93c044528e864344e6d27276

Quelldatensatz

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08710043B2