Tetrahydrofuran → Methyl 5-[5-(2,2'-dimethylbiphenyl-4-yl)-1,2,4-oxadiazol-3-yl]-2-hydroxybenzoate
Reaction equation
[NH2:1][C:2](=[N:14][OH:15])[C:3]1[CH:4]=[CH:5][C:6]([OH:13])=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9].CCN([CH:22]([CH3:24])[CH3:23])C(C)C.[CH2:25]1[CH2:29]O[CH2:27][CH2:26]1>O>[CH3:27][C:26]1[CH:2]=[C:3]([C:12]2[O:15][N:14]=[C:2]([C:3]3[CH:4]=[CH:5][C:6]([OH:13])=[C:7]([CH:12]=3)[C:8]([O:10][CH3:11])=[O:9])[N:1]=2)[CH:4]=[CH:5][C:25]=1[C:29]1[CH:8]=[CH:7][CH:6]=[CH:24][C:22]=1[CH3:23]Participants
Conditions
- Temperature
- 150 °C
Procedure
Under Argon atmosphere, Intermediate 3 (147.08 mg; 0.65 mmol) was stirred in anhydrous DCM (5 mL). Oxalyl chloride (57.75 μL; 0.68 mmol) was added followed by DMF (0.50 μL; 0.01 mmol). The reaction mixture was stirred 3 hours at RT. Solvents were evaporated to give 2,2′-dimethylbiphenyl-4-carbonyl chloride as a yellow oil. The latter was dissolved in anhydrous THF (3 mL), Intermediate 46 (136.62 mg; 0.65 mmol) and DIEA (221.08 μL; 1.30 mmol) were added under argon. The mixture was heated in the microwave at 150° C. for 15 min. The reaction mixture was diluted in water and extracted with EtOAc, the organic phase was then washed with NH4Cl, NaHCO3 and NaCl sat. solution. The organic layer was then dried over magnesium sulfate, filtered and concentrated, the crude product was purified by flash chromatography (c-hex/EtOAc: 9.5/0.5), affording the title compound. LC/MS (Method A): 398.9 (M−H)−, 400.8 (M+H)+. HPLC (Method A) Rt 6.37 min (Purity: 98.8%).
Workup
- extractionextracted with EtOAc
- washthe organic phase was then washed with NH4Cl, NaHCO3 and NaCl sat. solution
- dry with materialThe organic layer was then dried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
- customthe crude product was purified by flash chromatography (c-hex/EtOAc: 9.5/0.5)
Sources & evidence
- ORD record
- ord-e6a6dae620714768b8cfbf3834af9d9d
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08202865B2
Reaction notes
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