Pyridine → 5-cyclopropyl-N-(4-bromo-3-methylphenyl)-isoxazole-4-carboxamide
Reaction equation
[CH:1]1([C:4]2[O:8][N:7]=[CH:6][C:5]=2[C:9]([OH:11])=O)[CH2:3][CH2:2]1.S(Cl)(Cl)=O.[Br:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][C:18]=1[CH3:24].N1C=CC=CC=1>ClCCl.CO>[CH:1]1([C:4]2[O:8][N:7]=[CH:6][C:5]=2[C:9]([NH:21][C:20]2[CH:22]=[CH:23][C:17]([Br:16])=[C:18]([CH3:24])[CH:19]=2)=[O:11])[CH2:2][CH2:3]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
3.33 g (21.7 mmol) of 5-cyclopropylisoxazole-4-carboxylic acid and 25 ml of thionyl chloride were refluxed for 90 minutes and after the thionyl chloride was evaporated in vacuo, the residue was azeotroped twice with toluene. 4.0 g (21.7 mmol) of 4-bromo-3-methyl-aniline were dissolved in 125 ml of dry dichloromethane, cooled to 0° C. and the acid chloride and 2.4 g (30 mmol) of pyridine each dissolved in 10 ml of dichloromethane, were added dropwise simultaneously. After stirring for thirty minutes at 0° C., the reaction mixture was washed 3 times with 75 ml of brine, dried over MgSO4 and the dichloromethane was removed in vacuo to yield a brown oil. Flash column chromatography (2% MeOH, 98% CH2Cl2) yielded a pale brown oil which crystallized upon standing. Crystallization from ethanol/water yielded the desired product as cream needles melting at 133°-135° C.
Workup
- customafter the thionyl chloride was evaporated in vacuo
- customthe residue was azeotroped twice with toluene
- additionwere added dropwise simultaneously
- washthe reaction mixture was washed 3 times with 75 ml of brine
- dry with materialdried over MgSO4
- customthe dichloromethane was removed in vacuo
- customto yield a brown oil
- customcrystallized
- customCrystallization from ethanol/water
Sources & evidence
- ORD record
- ord-6d93a0017d0647d4aba92cdce87b71f1
- Source dataset
- uspto-grants-1996_04
- Patent number
- US05506249
Reaction notes
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