Potassium Carbonate → 3-[4-(5-Fluoro-2-methyl-phenoxymethyl)-phenyl]-isoxazole-5-carboxylic acid amide

HRID 929810Notes

Reaction equation

Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:13]=[C:12]([C:14]([NH2:16])=[O:15])[O:11][N:10]=2)=[CH:5][CH:4]=1.[F:17][C:18]1[CH:19]=[CH:20][C:21]([CH3:25])=[C:22]([OH:24])[CH:23]=1.C([O-])([O-])=O.[K+].[K+]>CC#N>[F:17][C:18]1[CH:19]=[CH:20][C:21]([CH3:25])=[C:22]([CH:23]=1)[O:24][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:13]=[C:12]([C:14]([NH2:16])=[O:15])[O:11][N:10]=2)=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a mixture of 3-(4-bromomethyl-phenyl)-isoxazole-5-carboxylic acid amide (which may be prepared as described in Preparation of Intermediate 14; 30 mg, 0.107 mmol) in CH3CN (2 mL) were added 5-fluoro-2-methylphenol (20 μL. 0.18 mmoL) and K2CO3 (30 mg, 0.22 mmol). The mixture was heated at 90° C. for 16 h and then evaporated to dryness. The residue was purified by chromatography (66-75% EtOAc/hexanes) to give 3-[4-(5-fluoro-2-methyl-phenoxymethyl)-phenyl]-isoxazole-5-carboxylic acid amide (24 mg, 69%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.38 (br. s., 1H), 8.01 (br. s., 1H), 7.93 (d, J=8.2 Hz, 2H), 7.52-7.65 (m, 3H), 7.16 (t, J=7.5 Hz, 1H), 6.92 (dd, J=11.3, 2.6 Hz, 1H), 6.67 (td, J=8.5, 2.7 Hz, 1H), 5.20 (s, 2H), 2.16 (s, 3H).

Workup

customevaporated to dryness
customThe residue was purified by chromatography (66-75% EtOAc/hexanes)

Sources & evidence

ORD record: ord-b8a8616fe10e436ba5d485470555f013
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296711B2

Reaction notes

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