Hydrochloric Acid → N-(2,4-Difluoro-3-formylphenyl)-1-propanesulfonamide

HRID 2387267Notes

Reaction equation

HRID 2387267 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[NH:21][S:22]([CH2:25][CH2:26][CH3:27])(=[O:24])=[O:23].CN(C)[CH:30]=[O:31].Cl>O1CCCC1.O>[F:13][C:14]1[C:19]([CH:30]=[O:31])=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[NH:21][S:22]([CH2:25][CH2:26][CH3:27])(=[O:24])=[O:23]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 53419004N-(2,4-Difluorophenyl)propane-1-sulfonamideHCID 178418339Butyllithium

Product 1

HCID 53419003N-(2,4-Difluoro-3-formylphenyl)-1-propanesulfonamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To diisopropyl amine (0.210 mL, 1.49 mmol) in tetrahydrofuran (3 mL) was added n-butyllithium (2.50 M in hexane, 0.600 mL, 1.49 mmol) at −78° C. under an atmosphere of nitrogen. After 30 minutes, propane-1-sulfonic acid (2,4-difluoro-phenyl)-amide (9, 113 mg, 0.480 mmol) in tetrahydrofuran (2 mL) was added at −78° C. under am atmosphere of nitrogen. After 1 hour, N,N-dimethylformamide (0.050 mL, 0.64 mmol) was added. The reaction was stirred for 1 hour, then allowed to come to room temperature for 15 minutes. The reaction was poured into water, acidified with 1M HCl (aq.) to pH=1, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated and purified by silica gel column chromatography eluting with 30% ethyl acetate in hexane to give a solid (10, 25 mg, 20%). MS (ESI) [M−H+]−=262.0.

Workup

  1. waitAfter 1 hour
  2. waitto come to room temperature for 15 minutes
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltrated
  7. concentrationThe filtrate was concentrated
  8. custompurified by silica gel column chromatography
  9. washeluting with 30% ethyl acetate in hexane
  10. customto give a solid (10, 25 mg, 20%)

Sources & evidence

ORD record
ord-84ff9cd72d6945ec86c3b38bf43541ae
Source dataset
uspto-grants-2012_09
Patent number
US08268858B2

Reaction notes

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