Stannane, tributyl-(1Z)-1-propen-1-yl- → (Z)-methyl 4-amino-6-chloro-5-fluoro-3-(prop-1-en-1-yl)picolinate

HRID 75098Notes

Reaction equation

HRID 75098 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]=1I.[CH2:15]([Sn](CCCC)(CCCC)/C=C/C)[CH2:16][CH2:17]C>ClC(Cl)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[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:15]=[CH:16]\[CH3:17]

Participants

5

Reactant 2

HCID 5315049Stannane, tributyl-(1Z)-1-propen-1-yl-HCID 86668303Methyl 4-amino-6-chloro-5-fluoro-3-iodopicolinate

Product 1

HCID 86668304(Z)-methyl 4-amino-6-chloro-5-fluoro-3-(prop-1-en-1-yl)picolinate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

Methyl 4-amino-6-chloro-5-fluoro-3-iodopicolinate (0.4 g, 1.210 mmol), (E)-tributyl(prop-1-en-1-yl)stannane (0.481 g, 1.452 mmol), and bis(triphenylphosphine)palladium(II) chloride (0.085 g, 0.121 mmol) in dichloroethane (2.42 mL) were irradiated at 120° C. for 30 min in a microwave reactor. Celite was then added to the reaction mixture and the solvent was removed under vacuum. The crude product was first purified by flash column chromatography (SiO2, hexane/EtOAc gradient) then by reverse phase HPLC to afford the title compound as an orange oil: 1H NMR (400 MHz, CDCl3) δ 6.39 (dq, J=11.1, 1.7 Hz, 1H), 6.07 (dq, J=11.2, 6.9 Hz, 1H), 4.64 (s, 2H), 3.89 (s, 3H), 1.55 (dd, J=6.9, 1.7 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −139.48; EIMS m/z 245 ([M+H]+).

Workup

  1. additionCelite was then added to the reaction mixture
  2. customthe solvent was removed under vacuum
  3. customThe crude product was first purified by flash column chromatography (SiO2, hexane/EtOAc gradient)

Sources & evidence

ORD record
ord-3ccd9539ee194f42886233c03c80a69f
Source dataset
uspto-grants-2014_09
Patent number
US08835409B2

Reaction notes

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