Phosphorus tribromide → 5-(Bromomethyl)-4-chloro-2-fluorobenzenesulfonamide

HRID 83912Notes

Reaction equation

HRID 83912 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]=1

Participants

4

Reactant 2

HCID 24614Phosphorus tribromideHCID 667404624-Chloro-2-fluoro-5-(hydroxymethyl)benzenesulfonamide

Product 1

HCID 667407195-(Bromomethyl)-4-chloro-2-fluorobenzenesulfonamideYield 88.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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).

Workup

  1. customThe reaction was carefully quenched with H2O
  2. custompartitioned between THF and brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-974c760498984417a4438c27d6b4ac5b
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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