2-Chloro-4-fluoro-5-sulfamoylbenzoic acid → 4-Chloro-2-fluoro-5-(hydroxymethyl)benzenesulfonamide

HRID 83911Notes

Reaction equation

HRID 83911 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([S:12](=[O:15])(=[O:14])[NH2:13])=[CH:7][C:3]=1[C:4](O)=[O:5]>C1COCC1>[Cl:1][C:2]1[C:3]([CH2:4][OH:5])=[CH:7][C:8]([S:12]([NH2:13])(=[O:14])=[O:15])=[C:9]([F:11])[CH:10]=1

Participants

3

Reactant 1

HCID 42415462-Chloro-4-fluoro-5-sulfamoylbenzoic acid

Product 1

HCID 667404624-Chloro-2-fluoro-5-(hydroxymethyl)benzenesulfonamideYield 62.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

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 mixture was quenched with MeOH
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by chromatography (silica, EtOAc-Hex)

Sources & evidence

ORD record
ord-8ea648f88bbb46a983e2607958113f3e
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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