4-Methoxyphenol → 3-[4-(4-Methoxy-phenoxymethyl)-phenyl]-isoxazole-5-carboxylic acid amide

HRID 929797Notes

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

Participants

Conditions

Temperature: 85 °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 4-methoxyphenol (24 mg, 0.22 mmol) and K2CO3 (30 mg, 0.22 mmol). The mixture was heated at 85° C. for 16 h and then evaporated to dryness. The residue was purified by chromatography (66-75% EtOAc/hexanes) to give 3-[4-(4-methoxy-phenoxymethyl)-phenyl]-isoxazole-5-carboxylic acid amide (12 mg, 35%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.38 (br. s., 1H), 8.00 (br. s., 1H), 7.90 (d, J=8.4 Hz, 2H), 7.52-7.64 (m, 3H), 6.90-7.00 (m, 1H), 6.81-6.89 (m, 1H), 5.11 (s, 1H), 3.26-3.34 (m, 3H).

Workup

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

Sources & evidence

ORD record: ord-d39719fe5a294191ae3774a730ca04f5
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296711B2

Reaction notes

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