Water → (E)-methyl 4-amino-6-chloro-3-(2-chlorovinyl)-5-fluoropicolinate

HRID 75101Notes

Reaction equation

[NH2:1][C:2]1[C:7]([F:8])=[C:6]([Cl:9])[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1/[CH:14]=[CH:15]/[Si](C)(C)C.[Cl:20]N1C(=O)CCC1=O.O>CN(C=O)C>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([Cl:9])[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1/[CH:14]=[CH:15]/[Cl:20]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of (E)-methyl 4-amino-6-chloro-5-fluoro-3-(2-(trimethylsilyl)vinyl)picolinate (176 mg, 0.581 mmol) in DMF (2.3 mL) was added N-chlorosuccinimide (116 mg, 0.872 mmol). The reaction mixture was stirred at 60° C. After 4 h, the observed conversion was ˜50%. At this point, the reaction mixture was poured into water (30 mL) and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash column chromatography (SiO2, hexane/EtOAc gradient) to afford the title compound (75 mg, 0.283 mmol, 48.7% yield) as an orange solid: mp 128-130° C.; 1H NMR (400 MHz, CDCl3) δ 6.97 (d, J=14.1 Hz, 1H), 6.45 (d, J=14.1 Hz, 1H), 4.73 (s, 2H), 3.93 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −138.17; ESIMS m/z 265 ([M]+).

Workup

extractionextracted with EtOAc (3×)
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by flash column chromatography (SiO2, hexane/EtOAc gradient)

Sources & evidence

ORD record: ord-46dba9492a7d4c6fbf6b2ecae1b603c8
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835409B2

Reaction notes

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