2-Chlorophenol → 3-[4-(2-Chloro-phenoxymethyl)-phenyl]-isoxazole-5-carboxylic acid amide

HRID 929790Notes

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.[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[OH:24].C([O-])([O-])=O.[K+].[K+]>CC#N>[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=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; 40 mg, 0.142 mmol) in CH3CN (2 mL) were added 2-chlorophenol (22 μL, 0.22 mmol) and K2CO3 (40 mg, 0.29 mmol). The mixture was heated at 90° C. for 4 h and then evaporated to dryness. The residue was purified by chromatography (66-75% EtOAc/hexanes) to give 3-[4-(2-chloro-phenoxymethyl)-phenyl]-isoxazole-5-carboxylic acid amide (37 mg, 79%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.39 (br. s., 1H), 8.01 (br. s., 1H), 7.94 (d, J=8.1 Hz, 2H), 7.61 (d, J=9.5 Hz, 3H), 7.44 (dd, J=8.1, 1.5 Hz, 1H), 7.19-7.35 (m, 2H), 6.92-7.01 (m, 1H), 5.29 (s, 2H).

Workup

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

Sources & evidence

ORD record: ord-a75722f35d2d408faf17d7148c95615b
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296711B2

Reaction notes

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