Thionyl Chloride → 3-Bromo-5-chloro-N-cyclopropyl-4-methylbenzamide
Reaction equation
BrC1C=C(C=C(Cl)C=1C)C(O)=O.S(Cl)(Cl)=O.[Br:17][C:18]1[CH:19]=[C:20]([CH:27]=[C:28]([Cl:31])[C:29]=1[CH3:30])[C:21]([NH:23][CH:24]1[CH2:26][CH2:25]1)=[O:22].ClC1C=C(C=CC=1C)C(NC1CC1)=O>>[Br:17][C:18]1[CH:19]=[C:20]([CH:27]=[C:28]([Cl:31])[C:29]=1[CH3:30])[C:21]([NH:23][CH:24]1[CH2:26][CH2:25]1)=[O:22]Participants
Conditions
- Temperature
- 90 °C
Procedure
3-Bromo-5-chloro-4-methylbenzoic acid (Intermediate 17, 310 mg, contaminated with 3-bromo-5-chloro-4-methylbenzoic acid) was mixed with thionyl chloride (3 ml) and the mixture heated at 90° C. for 2.5 hours. The excess thionyl chloride was evaporated under vacuum and the residue was dissolved in DCM (7.5 ml). Cyclopropylamine (0.2 ml) and sodium carbonate (500 mg) were added to the solution and the reaction stirred for 2 hours at room temperature. The reaction was filtered, the filtrate absorbed onto silica and applied to a SPE (Si, 10 g). The SPE was eluted with an ethyl acetate/cyclohexane gradient (p50% ethyl acetate) and the product fractions reduced to dryness under vacuum to give a mixture of 3-bromo-5-chloro-N-cyclopropyl-4-methylbenzamide/3-chloro-N-cyclopropyl-4-methylbenzamide (2:1).
Workup
- customThe excess thionyl chloride was evaporated under vacuum
- dissolutionthe residue was dissolved in DCM (7.5 ml)
- additionCyclopropylamine (0.2 ml) and sodium carbonate (500 mg) were added to the solution
- filtrationThe reaction was filtered
- customthe filtrate absorbed onto silica
- washThe SPE was eluted with an ethyl acetate/cyclohexane gradient (p50% ethyl acetate)
- customto give
Sources & evidence
- ORD record
- ord-6bf67fdb7750420e86f02f258fb4aa52
- Source dataset
- uspto-grants-2007_04
- Patent number
- US07208629B2
Reaction notes
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