Sulfuric Acid → 2-[(E)-2-(3-Butyl-5-methyl-isoxazol-4-yl)-vinyl]-thiazole-5-carboxylic acid isoprop-ylamide
Reaction equation
CO[C:3]([C:5]1[S:9][C:8]([CH2:10][CH:11]([C:13]2[C:14]([CH2:19][CH2:20][CH2:21][CH3:22])=[N:15][O:16][C:17]=2[CH3:18])O)=[N:7][CH:6]=1)=[O:4].S(=O)(=O)(O)O.[CH:28]([NH2:31])([CH3:30])[CH3:29]>>[CH:28]([NH:31][C:3]([C:5]1[S:9][C:8](/[CH:10]=[CH:11]/[C:13]2[C:14]([CH2:19][CH2:20][CH2:21][CH3:22])=[N:15][O:16][C:17]=2[CH3:18])=[N:7][CH:6]=1)=[O:4])([CH3:30])[CH3:29]Participants
4
Conditions
- Temperature
- 90 °C
Procedure
2-[2-(3-Butyl-5-methyl-isoxazol-4-yl)-2-hydroxy-ethyl]-thiazole-5-carboxylic acid methyl ester (30 mg, 0.092 mmol) was stirred with concentrated sulfuric acid (0.1 mL) for 30 min, then the reaction mixture quenched with saturated sodium bicarbonate solution and extracted with ethyl acetate. The combined organic phases were dried, filtered and concentrated, then dissolved in toluene (0.5 mL) and isopropylamine (22 mg, 0.37 mmol) and TBD (13 mg, 0.092 mmol) added. The reaction mixture was then heated at 90° C. for 15 h and then the reaction mixture was concentrated then purified by chromatography (silica, 0 to 3% methanol in dichloromethane) to give the title compound (10 mg, 34%) as a pale yellow oil. MS: m/e=334.3 [M+H]+.
Workup
- customthe reaction mixture quenched with saturated sodium bicarbonate solution
- extractionextracted with ethyl acetate
- customThe combined organic phases were dried
- filtrationfiltered
- concentrationconcentrated
- dissolutiondissolved in toluene (0.5 mL)
- concentrationthe reaction mixture was concentrated
- customthen purified by chromatography (silica, 0 to 3% methanol in dichloromethane)
Sources & evidence
- ORD record
- ord-c6e19bc3750246d38f9967bd195ec022
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08178522B2
Reaction notes
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