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

HRID 929796Notes

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:20]=[C:21]([OH:25])[CH:22]=[CH:23][CH:24]=1.C([O-])([O-])=O.[K+].[K+]>CC#N>[CH3:17][O:18][C:19]1[CH:20]=[C:21]([CH:22]=[CH:23][CH:24]=1)[O:25][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: 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 3-methoxyphenol (21 μL, 0.19 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-(3-methoxy-phenoxymethyl)-phenyl]-isoxazole-5-carboxylic acid amide (20 mg, 58%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.38 (br. s., 1H), 8.00 (br. s., 1H), 7.91 (d, J=8.1 Hz, 2H), 7.54-7.62 (m, 3H), 7.18 (t, J=7.9 Hz, 1H), 6.47-6.64 (m, 3H), 5.16 (s, 2H), 3.26-3.33 (m, 3H).

Workup

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

Sources & evidence

ORD record: ord-0da7d62efdac42568ca837eba3c6b7c0
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296711B2

Reaction notes

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