Potassium Carbonate → 3-[4-(2-Trifluoromethyl-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amide

HRID 929788Notes

Reaction equation

[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([C:13]([NH2:15])=[O:14])[O:10][N:9]=2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]([F:33])([F:32])[F:31]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:31][C:30]([F:32])([F:33])[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[CH2:23][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:12]=[C:11]([C:13]([NH2:15])=[O:14])[O:10][N:9]=2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 40 °C

Procedure

3-(4-Hydroxy-phenyl)-isoxazole-5-carboxylic acid amide (which may be prepared as described in Preparation of Intermediate 2; 40 mg, 0.196 mmol) was dissolved in DMF (1 mL). K2CO3 (19 mg, 0.14 mmol), tetrabutylammonium iodide (7 mg, 0.02 mmol), and 1-chloromethyl-2-trifluoromethyl-benzene (36 μL, 0.25 mmol) were added. The reaction mixture was heated at 40° C. for 14 h. The reaction mixture was partitioned between H2O (5 mL) and EtOAc (5 mL). The organic layer was dried (Na2SO4), filtered, evaporated, and purified by chromatography (30% EtOAc/hexanes) to give 3-[4-(2-trifluoromethyl-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amide (1.3 mg, 2%) as a white solid. HRMS Calcd. for C18H14F3N2O3 (M+H)+, 363.0951. Found: 363.0950.

Workup

customThe reaction mixture was partitioned between H2O (5 mL) and EtOAc (5 mL)
dry with materialThe organic layer was dried (Na2SO4)
filtrationfiltered
customevaporated
custompurified by chromatography (30% EtOAc/hexanes)

Sources & evidence

ORD record: ord-4ffa20c1ded541249e1834712c4d64e6
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296711B2

Reaction notes

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