Ammonia → Methyl 5-chloro-2-[(5-chloropyridin-2-yl)oxy]benzoate

HRID 1293268Notes

Reaction equation

N[C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:10]=2[C:11]([O:13][CH3:14])=[O:12])=[N:6][CH:7]=1.N([O-])=O.[Na+].[Cl-:24].N>Cl.O.CC(C)=O>[Cl:19][C:16]1[CH:17]=[CH:18][C:9]([O:8][C:5]2[CH:4]=[CH:3][C:2]([Cl:24])=[CH:7][N:6]=2)=[C:10]([CH:15]=1)[C:11]([O:13][CH3:14])=[O:12]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methyl 2-[(5-aminopyridin-2-yl)oxy]-5-chlorobenzoate (step 2 of Example 101, 1.00 g, 3.6 mmol) in 0.66 M hydrochloric acid (11 mL) was added sodium nitrite (252 mg, 3.6 mmol) in water (5 mL) at 0° C. The reaction mixture was stirred for 30 mim at 0° C. The mixture was added dropwise to a stirred suspension of cupper(II) chloride (1.21 g, 9.0 mmol) in acetone (18 mL) and water (5.4 mL). The whole was stirred at 50° C. for 30 min. Then the reaction mixture was poured into water and it was added ammonia solution. The aqueous mixture was extracted with ethyl acetate. The organic phase was washed with brine, dried over sodium sulfate, and concentrated. The residue was purified by flush column chromatography on silica gel eluting with hexane/ethyl acetate (20/1) to afford 347 mg (32%) of the title compound: 1H-NMR (CDCl3) δ 8.00 (1H, d, J=2.8 Hz), 7.99 (1H, d, J=2.8 Hz), 7.67 (1H, dd, J=8.7, 2.8 Hz), 7.55 (1H, dd, J=8.6, 2.8 Hz), 7.14 (1H, d, J=8.6 Hz), 6.97 (1H, d, J=8.7 Hz), 3.72 (3H, s).

Workup

stirringThe whole was stirred at 50° C. for 30 min
extractionThe aqueous mixture was extracted with ethyl acetate
washThe organic phase was washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated
customThe residue was purified
customby flush column chromatography on silica gel eluting with hexane/ethyl acetate (20/1)

Sources & evidence

ORD record: ord-d0efa75d49124d738fc9228d49ec26f0
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07238714B2

Reaction notes

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