4-Fluorophenylboronic acid → Methyl 3-amino-6-(4-fluorophenyl)-5-(trifluoromethyl)picolinate

HRID 2173722Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C:10]([NH2:11])=[CH:9][C:8]([C:12]([F:15])([F:14])[F:13])=[C:7](Br)[N:6]=1)=[O:4].[F:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1>C1COCC1.C([O-])([O-])=O.[Cs+].[Cs+]>[NH2:11][C:10]1[C:5]([C:3]([O:2][CH3:1])=[O:4])=[N:6][C:7]([C:21]2[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=2)=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:9]=1

Participants

Conditions

Temperature: 160 °C

Procedure

3-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (Intermediate 3D) (200 mg, 0.669 mmol), 4-fluorophenylboronic acid (94 mg, 0.669 mmol) and 1,1′bis(diphenylphosphoshio)ferrocene palladium dichloride (Apollo) were suspended in THF (2 ml) and 1M Cs2CO3 (0.667 ml). The vial was flushed with N2, sealed and heated at 160° C. for 15 minutes using microwave radiation. The reaction mixture was partitioned between EtOAc (50 ml) and water (50 ml). The organic portion was separated and washed with brine (30 ml), dried over MgSO4, filtered and concentrated in vacuo. Purification by chromatography on silica eluting with 0-80% EtOAc in iso-hexane afforded the title compound;

Workup

customThe vial was flushed with N2
customsealed
customThe reaction mixture was partitioned between EtOAc (50 ml) and water (50 ml)
customThe organic portion was separated
washwashed with brine (30 ml)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by chromatography on silica eluting with 0-80% EtOAc in iso-hexane

Sources & evidence

ORD record: ord-16c699a5eab54d668727863b1187e505
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09056867B2

Reaction notes

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