Phosphorus tribromide → 5-(Bromomethyl)-4-chloro-2-fluorobenzenesulfonamide
Reaction equation
[Cl:1][C:2]1[C:7]([CH2:8]O)=[CH:6][C:5]([S:10]([NH2:13])(=[O:12])=[O:11])=[C:4]([F:14])[CH:3]=1.P(Br)(Br)[Br:16]>C(Cl)Cl>[Br:16][CH2:8][C:7]1[C:2]([Cl:1])=[CH:3][C:4]([F:14])=[C:5]([S:10]([NH2:13])(=[O:12])=[O:11])[CH:6]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 2-chloro-4-fluoro-5-sulfamoylbenzoic acid (3.2 g, 12.65 mmol) in THF (10 mL) was added 1M BH3 THF (38 mL, 38.0 mmol). After stirring 12 h, the reaction mixture was quenched with MeOH and concentrated in vacuo. The residue was purified by chromatography (silica, EtOAc-Hex) to afford 4-chloro-2-fluoro-5-(hydroxymethyl)benzenesulfonamide (1.9 g). To a suspension of 4-chloro-2-fluoro-5-(hydroxymethyl)benzenesulfonamide (1.78 g, 7.43 mmol) in DCM (10 mL) was added PBr3 (2.21 g, 8.17 mmol). The reaction was stirred for 24 h when it was determined to be complete by GCMS. The reaction was carefully quenched with H2O and then partitioned between THF and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo to afford 5-(bromomethyl)-4-chloro-2-fluorobenzenesulfonamide (1.98 g) as an off-white solid. 1H-NMR (DMSO-d6, 400 MHz) δ 8.08 (d, J=7.8 Hz, 1H), 7.84 (s, 2H), 7.80 (d, J=9.9 Hz, 1H), 4.83 (s, 2H).