O-Cresol → 3-(4-o-Tolyloxymethyl-phenyl)-isoxazole-5-carboxylic acid amide

HRID 929793Notes

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.[C:17]1([CH3:24])[C:22]([OH:23])=[CH:21][CH:20]=[CH:19][CH:18]=1.C([O-])([O-])=O.[K+].[K+]>CC#N>[C:17]1([CH3:24])[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=1[O:23][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 o-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-o-tolyloxymethyl-phenyl)-isoxazole-5-carboxylic acid amide (21 mg, 64%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.38 (br. s., 1H), 8.00 (br. s., 1H), 7.92 (d, J=8.1 Hz, 2H), 7.53-7.67 (m, 3H), 7.05-7.20 (m, 2H), 6.99 (d, J=7.7 Hz, 1H), 6.74-6.90 (m, 1H), 5.19 (s, 2H), 2.21 (s, 3H).

Workup

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

Sources & evidence

ORD record: ord-554e294941ed417fa28580d7eac39a60
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296711B2

Reaction notes

Loading…