Potassium Carbonate → tert-Butyl 4-(5-chloro-6-methoxypyridin-3-yloxy)-2,5-difluorobenzoate

HRID 2048047Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([OH:10])[CH:5]=[N:6][C:7]=1[O:8][CH3:9].[F:11][C:12]1[CH:24]=[C:23](F)[C:22]([F:26])=[CH:21][C:13]=1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([O:10][C:23]2[C:22]([F:26])=[CH:21][C:13]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])=[C:12]([F:11])[CH:24]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9]

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of 5-chloro-6-methoxypyridin-3-ol (Preparation 77, 100 mg, 0.627 mmol), tert-butyl 2,4,5-trifluorobenzoate (Preparation 6, 147 mg, 0.633 mmol), and potassium carbonate (260 mg, 1.88 mmol) in DMSO (5 ml) was stirred overnight at 25° C. under a nitrogen atmosphere. The reaction was diluted with water (50 mL) and extracted with EtOAc (3×30 mL). The combined organics were washed with aqueous sodium hydroxide solution (1.0 M, 30 mL), brine (2×40 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude was purified by silica gel chromatography eluting with 5% EtOAc in heptane to afford the title compound as a white solid (65 mg, 28%):

Workup

extractionextracted with EtOAc (3×30 mL)
washThe combined organics were washed with aqueous sodium hydroxide solution (1.0 M, 30 mL), brine (2×40 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude was purified by silica gel chromatography
washeluting with 5% EtOAc in heptane

Sources & evidence

ORD record: ord-596c0232d7aa47f6bf9d38f338a83156
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08592629B2

Reaction notes

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