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

HRID 1627274Notes

Reaction equation

HRID 1627274 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-7b58586952ca4c49a812e05a764156d2
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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