Acetonitrile → Methyl 4-amino-6-(2,3-difluoro-4-(trifluoromethyl)phenyl)-5-fluoro-3-vinylpicolinate

HRID 516557Notes

Reaction equation

[F:1][C:2]1[C:7]([F:8])=[C:6]([C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:4][C:3]=1B1OC(C)(C)C(C)(C)O1.[NH2:22][C:23]1[C:28]([F:29])=[C:27](Cl)[N:26]=[C:25]([C:31]([O:33][CH3:34])=[O:32])[C:24]=1[CH:35]=[CH2:36].C(=O)([O-])[O-].[Na+].[Na+].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>[NH2:22][C:23]1[C:28]([F:29])=[C:27]([C:3]2[CH:4]=[CH:5][C:6]([C:9]([F:10])([F:11])[F:12])=[C:7]([F:8])[C:2]=2[F:1])[N:26]=[C:25]([C:31]([O:33][CH3:34])=[O:32])[C:24]=1[CH:35]=[CH2:36]

Participants

Conditions

Temperature: 120 °C

Procedure

In a microwave vessel, a suspension of 2-(2,3-difluoro-4-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (commercially available) (0.641 g, 2.081 mmol), methyl 4-amino-6-chloro-5-fluoro-3-vinylpicolinate (Head G) (0.4 g, 1.734 mmol), bis(triphenyl phosphine)palladium(II) chloride (0.122 g, 0.173 mmol) and sodium carbonate (0.368 g, 3.47 mmol) in a 3:1 mixture of acetonitrile (3.25 mL) and water (1.084 mL) was stirred under microwave irradiation (120° C., 20 min). The reaction mixture was poured into an 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 preparative reverse phase HPLC (water/acetonitrile gradient) to afford the title compound as a brown solid (0.163 g, 0.433 mmol, 24.98%).

Workup

extractionwas extracted with EtOAc (3×)
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by preparative reverse phase HPLC (water/acetonitrile gradient)

Sources & evidence

ORD record: ord-39738c9841774ed2afee354b69b744e9
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09113629B2

Reaction notes

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