Borane;tetrahydrofuran → 4-Chloro-2-fluoro-5-(hydroxymethyl)benzenesulfonamide

HRID 1627273Notes

Reaction equation

HRID 1627273 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].B.C1COCC1>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

4

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 42415462-Chloro-4-fluoro-5-sulfamoylbenzoic acid

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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-b344ae082dcf4379b594a7dfffa222f3
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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