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

HRID 929789Notes

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+].Br[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[S:30]([CH3:33])(=[O:32])=[O:31]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:33][S:30]([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)(=[O:31])=[O:32]

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; 50 mg, 0.245 mmol) was dissolved in DMF (1.5 mL). K2CO3 (42 mg, 0.30 mmol), tetrabutylammonium iodide (14 mg, 0.038 mmol), and 1-bromomethyl-2-methylsulfonyl-benzene (which is available from Combi-Blocks; 62 mg, 0.25 mmol) were added. The reaction mixture was heated at 40° C. for 13 h. The reaction mixture was cooled to room temperature and partitioned between H2O (5 mL) and EtOAc (5 mL). The organic layer was dried (Na2SO4), filtered, evaporated, and purified twice by chromatography (40-60% EtOAc/hexanes) to give 3-[4-(2-methanesulfonyl-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amide (3 mg, 3%) as a white powder. HRMS Calcd. for C18H17N2O5S (M+H)+, 373.0853. Found: 373.0854.

Workup

temperatureThe reaction mixture was cooled to room temperature
custompartitioned between H2O (5 mL) and EtOAc (5 mL)
dry with materialThe organic layer was dried (Na2SO4)
filtrationfiltered
customevaporated
custompurified twice by chromatography (40-60% EtOAc/hexanes)

Sources & evidence

ORD record: ord-e3fc7104554e46f89e32614ad9c30756
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296711B2

Reaction notes

Loading…