Acetonitrile → Methyl 4-amino-6-(4-aminophenyl)-5-fluoro-3-vinylpicolinate

HRID 516558Notes

Reaction equation

HRID 516558 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=2)O1.[NH2:17][C:18]1[C:23]([F:24])=[C:22](Cl)[N:21]=[C:20]([C:26]([O:28][CH3:29])=[O:27])[C:19]=1[CH:30]=[CH2:31].[F-].[K+].C(#N)C>[Cl-].[Na+].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.O>[NH2:17][C:18]1[C:23]([F:24])=[C:22]([C:9]2[CH:10]=[CH:11][C:12]([NH2:13])=[CH:14][CH:15]=2)[N:21]=[C:20]([C:26]([O:28][CH3:29])=[O:27])[C:19]=1[CH:30]=[CH2:31]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 522689Potassium FluorideHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 86668309Methyl 4-amino-6-chloro-5-fluoro-3-vinylpicolinate

Product 1

HCID 90409711Methyl 4-amino-6-(4-aminophenyl)-5-fluoro-3-vinylpicolinateYield 89%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
120 °C

Procedure

In a microwave vessel, a suspension of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (commercially available) (0.617 g, 2.82 mmol), methyl 4-amino-6-chloro-5-fluoro-3-vinylpicolinate (Head G) (0.5 g, 2.168 mmol), bis(triphenyl phosphine)palladium(II) chloride (0.152 g, 0.217 mmol) and potassium fluoride (0.327 g, 5.64 mmol) in a 1:1 mixture of acetonitrile (3.61 mL) and water (3.61 mL) was stirred under microwave irradiation (120° C., 20 min). The reaction mixture was poured into a half saturated brine solution and was extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (SiO2 24 g, hexanes/EtOAc gradient) to afford the title compound as a yellow solid (0.552 g, 89%) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ 7.60-7.58 (m, 2H), 6.72 (dd, J=17.7, 11.5 Hz, 1H), 6.65-6.58 (m, 2H), 6.24 (s, 2H), 5.47 (s, 2H), 5.45 (dd, J=11.5, 1.2 Hz, 1H), 5.38 (dd, J=17.7, 1.2 Hz, 1H), 3.77 (s, 3H); 19F NMR (376 MHz, DMSO-d6) δ −146.62; ESIMS m/z 286 ([M−H]−).

Workup

  1. extractionwas extracted with EtOAc (3×)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography (SiO2 24 g, hexanes/EtOAc gradient)

Sources & evidence

ORD record
ord-a226a433cf2445f0b775ea7a96e628e8
Source dataset
uspto-grants-2015_08
Patent number
US09113629B2

Reaction notes

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