Tributylvinyltin → Methyl 4-amino-6-chloro-5-fluoro-3-vinylpicolinate

Temperature

70 °C

Methyl 4-amino-6-chloro-5-fluoro-3-iodopicolinate (7.05 g, 21.33 mmol, prepared as described in Epp et al., WO 2013003740 A1) and vinyltri-n-butyltin (7.52 mL, 25.6 mmol) were suspended in 1,2-dichloroethane (71.1 mL) and the mixture was degassed with Argon for 10 min. Bis(triphenylphosphine)palladium(II) chloride (1.497 g, 2.133 mmol) was then added and the reaction mixture was stirred at 70° C. overnight (clear orange solution). The reaction was monitored by gas chromatography-mass spectrometry (GC-MS). After 20 h, the reaction mixture was concentrated, adsorbed onto Celite, and purified by column chromatography (SiO2; hexanes/ethyl acetate gradient) to afford the title compound as a light brown solid (3.23 g, 65.7%): mp 99-100° C.; 1H NMR (400 MHz, CDCl3) δ 6.87 (dd, J=18.1, 11.6 Hz, 1H), 5.72 (dd, J=11.5, 1.3 Hz, 1H), 5.52 (dd, J=18.2, 1.3 Hz, 1H), 4.79 (s, 2H), 3.91 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −138.79 (s); EIMS m/z 230.

1. customthe mixture was degassed with Argon for 10 min
2. waitAfter 20 h
3. concentrationthe reaction mixture was concentrated
4. custompurified by column chromatography (SiO2; hexanes/ethyl acetate gradient)

ORD record

ord-a7f303bf7df3446f8218676bcff25e44

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09149038B2