Tetrafluoroboric acid → Methyl 5-chloro-2-[(5-fluoropyridin-2-yl)oxy]benzoate

HRID 1293265Notes

Reaction equation

N([O-])=O.[Na+].N[C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:14]=2[C:15]([O:17][CH3:18])=[O:16])=[N:10][CH:11]=1.[F:24][B-](F)(F)F.[H+]>O>[Cl:23][C:20]1[CH:21]=[CH:22][C:13]([O:12][C:9]2[CH:8]=[CH:7][C:6]([F:24])=[CH:11][N:10]=2)=[C:14]([CH:19]=1)[C:15]([O:17][CH3:18])=[O:16]

Participants

Conditions

Temperature: 140 °C

Procedure

To a solution of sodium nitrite (224 mg, 3.25 mmol) in water (5 mL) was added methyl 2-[(5-aminopyridin-2-yl)oxy]-5-chlorobenzoate (907 mg, 3.25 mmol) and 48% tetrafluoroboric acid in water (5 mL) at 0° C. The reaction mixture was stirred for 5 h. The resulting precipitate was collected by filtration and dried under reduced pressure at room temperature. To the solids of tetrafluoroborate were added chlorobenzene (5 mL) and the mixture was heated at 140° C. for 40 min. The reaction mixture was diluted with ethyl acetate. The solution was washed with brine and concentrated. The residue was purified by flush column chromatography on silica gel eluting with hexane/ethyl acetate (8/1) to afford 382 mg (42%) of the title compound: 1H-NMR (CDCl3) δ 7.98 (1H, d, J=2.8 Hz), 7.90 (1H, d, J=3.1 Hz), 7.59–7.41 (2H, m), 7.14 (1H, d, J=8.6 Hz), 6.99 (1H, dd, J=8.9, 3.5 Hz), 3.72 (3H, s).

Workup

filtrationThe resulting precipitate was collected by filtration
customdried under reduced pressure at room temperature
additionTo the solids of tetrafluoroborate were added chlorobenzene (5 mL)
additionThe reaction mixture was diluted with ethyl acetate
washThe solution was washed with brine
concentrationconcentrated
customThe residue was purified
customby flush column chromatography on silica gel eluting with hexane/ethyl acetate (8/1)

Sources & evidence

ORD record: ord-a82fe8ed802d46da97da38b58e32a54e
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07238714B2

Reaction notes

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