M-Cresol → 3-(4-m-Tolyloxymethyl-phenyl)-isoxazole-5-carboxylic acid amide

HRID 929794Notes

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.[CH:17]1[C:22]([OH:23])=[CH:21][CH:20]=[CH:19][C:18]=1[CH3:24].C([O-])([O-])=O.[K+].[K+]>CC#N>[C:18]1([CH3:24])[CH:19]=[CH:20][CH:21]=[C:22]([O:23][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:17]=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 m-cresol (20 mg, 0.185 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-m-tolyloxymethyl-phenyl)-isoxazole-5-carboxylic acid amide (20 mg, 61%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.38 (br. s., 1H), 8.00 (br. s., 1H), 7.86-7.95 (m, 3H), 7.53-7.63 (m, 4H), 7.11-7.22 (m, 1H), 6.69-6.89 (m, 3H), 5.15 (s, 2H), 2.26 (s, 3H).

Workup

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

Sources & evidence

ORD record: ord-ca6975a1e1434c6fba2dc1963ae0197d
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296711B2

Reaction notes

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