Methyl iodide → N-(4-chloro-3-methyl-5-isoxazolyl)-3-sulfamoyl-5-methyl-2-thiophenecarboxylic acid
Reaction equation
[Cl:1][C:2]1[C:3]([CH3:19])=[N:4][O:5][C:6]=1[NH:7][S:8]([C:11]1[CH:15]=[CH:14][S:13][C:12]=1[C:16]([OH:18])=[O:17])(=[O:10])=[O:9].[Li][CH2:21]CCC.IC>O1CCCC1>[Cl:1][C:2]1[C:3]([CH3:19])=[N:4][O:5][C:6]=1[NH:7][S:8]([C:11]1[CH:15]=[C:14]([CH3:21])[S:13][C:12]=1[C:16]([OH:18])=[O:17])(=[O:10])=[O:9]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of N-(4-chloro-3-methyl-5-isoxazolyl)-3-sulfamoyl-2-thiophenecarboxylic acid (6 g, 18.60 mmol) in anhydrous tetrahydrofuran (240 mL) at −78° C. and under nitrogen was added nBuLi (2.5 M in hexane, 30 mL, 74.4 mmol). The mixture was stirred at this temperature for 2 h before the addition of iodomethane (6.6 g, 74.4 mmol). The mixture was then poured into crushed ice and then allowed to warm to room temperature. After acidification with concentrated HCl to pH ˜1, the mixture was extracted with ethyl acetate (2×200 mL). The organic layers were combined, dried (MgSO4), the solids were filtered and the filtrate was concentrated to give N-(4-chloro-3-methyl-5-isoxazolyl)-3-sulfamoyl-5-methyl-2-thiophenecarboxylic acid and the starting material in about a 2:1 ratio (8.5 g combined weight).
Workup
- additionThe mixture was then poured
- custominto crushed ice
- extractionAfter acidification with concentrated HCl to pH ˜1, the mixture was extracted with ethyl acetate (2×200 mL)
- dry with materialdried (MgSO4)
- filtrationthe solids were filtered
- concentrationthe filtrate was concentrated
Sources & evidence
- ORD record
- ord-04ae8590f6254e00892d443fcd9bf15b
- Source dataset
- uspto-grants-2002_08
- Patent number
- US06432994B1
Reaction notes
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