Acetonitrile → HCID 90408697, compound

HRID 516561Notes

Reaction equation

HRID 516561 reaction equation
[F-].[K+].[NH2:3][C:4]1[C:9]([F:10])=[C:8](Cl)[N:7]=[C:6]([C:12]([O:14][CH3:15])=[O:13])[C:5]=1[CH:16]=[CH2:17].CC1(C)C(C)(C)OB([C:26]2[CH:33]=[CH:32][C:29]([CH:30]=[O:31])=[CH:28][CH:27]=2)O1.C(#N)C>C(Cl)Cl.O.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>[NH2:3][C:4]1[C:9]([F:10])=[C:8]([C:26]2[CH:33]=[CH:32][C:29]([CH:30]=[O:31])=[CH:28][CH:27]=2)[N:7]=[C:6]([C:12]([O:14][CH3:15])=[O:13])[C:5]=1[CH:16]=[CH2:17]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 522689Potassium FluorideHCID 27695364-Formylphenylboronic acid pinacol esterHCID 86668309Methyl 4-amino-6-chloro-5-fluoro-3-vinylpicolinate

Product 1

HCID 90408697HCID 90408697, compoundYield 97.5%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a 5-mL microwave safe vial was added potassium fluoride (0.378 g, 6.50 mmol), methyl 4-amino-6-chloro-5-fluoro-3-vinylpicolinate (0.5 g, 2.168 mmol), bis(triphenylphosphine)palladium(II) chloride (0.152 g, 0.217 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (0.528 g, 2.276 mmol). A mixture of water (1 mL) and acetonitrile (2 mL) was added and the reaction was capped and placed in a Biotage Initiator™ microwave reactor for 20 min at 115° C., with external IR-sensor temperature monitoring from the side of the vessel. Upon cooling to room temperature, the reaction mixture was diluted with CH2Cl2 (25 mL) and water (25 mL) and the organic layer was filtered through a cotton plug. An additional extraction using EtOAc (25 mL) was combined with the CH2Cl2 and dried over Na2SO4 (50 g). Following filtration of the combined organics through a cotton plug and concentration on a rotary evaporator, the residue was purified using a Teledyne ISCO purification system with a gradient eluent system of CH2Cl2 and EtOAc to yield the title compound as a white solid (635 mg): 1H NMR (400 MHz, CDCl3) δ 10.08 (s, 1H), 8.13 (dd, J=8.3, 1.6 Hz, 2H), 8.03-7.93 (m, 2H), 6.91 (ddd, J=18.1, 11.6, 0.5 Hz, 1H), 5.73 (dd, J=11.5, 1.4 Hz, 1H), 5.60 (dd, J=18.1, 1.4 Hz, 1H), 4.77 (s, 2H), 3.94 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −143.49; ESIMS m/z 301 ([M+H]+).

Workup

  1. additionwas added
  2. customthe reaction was capped
  3. filtrationthe organic layer was filtered through a cotton plug
  4. extractionAn additional extraction
  5. dry with materialdried over Na2SO4 (50 g)
  6. filtrationfiltration of the
  7. concentrationcombined organics through a cotton plug and concentration
  8. customon a rotary evaporator
  9. customthe residue was purified
  10. customa Teledyne ISCO purification system with a gradient eluent system of CH2Cl2 and EtOAc

Sources & evidence

ORD record
ord-d87fce373ac541c1976e08eed4adf297
Source dataset
uspto-grants-2015_08
Patent number
US09113629B2

Reaction notes

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