Pyridine → 3-(2,5-Difluoro-benzenesulfonylamino)-2-fluoro-benzoic acid methyl ester

HRID 1187302Notes

Reaction equation

HRID 1187302 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH2:10])[C:5]=1[F:11].N1C=CC=CC=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1[S:27](Cl)(=[O:29])=[O:28]>ClCCl>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][S:27]([C:21]2[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=2[F:19])(=[O:29])=[O:28])[C:5]=1[F:11]

Participants

5

Reactant 3

HCID 1049PyridineHCID 27369112,5-Difluorobenzenesulfonyl chlorideHCID 46311080Methyl 3-amino-2-fluorobenzoate

Product 1

HCID 583169963-(2,5-Difluoro-benzenesulfonylamino)-2-fluoro-benzoic acid methyl esterYield 43.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 3-amino-2-fluoro-benzoic acid methyl ester (72, 1.08 g, 6.4 mmol) in 40.64 mL of dichloromethane, pyridine (1.29 mL, 16 mmol) is added, followed by 2,5-difluorobenzenesulfonyl chloride (73, 3.391 g, 16 mmol). The reaction is stirred at room temperature overnight, then quenched with 1M aqueous hydrochloric acid. The organic layer is removed and the aqueous layer is extracted with dichloromethane. The organic layers are combined and washed with brine, then dried over sodium sulfate, filtered and the filtrate is concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with ethyl acetate and hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (74, 0.956 g). MS (ESI) [M−H+]−=344.

Workup

  1. customquenched with 1M aqueous hydrochloric acid
  2. customThe organic layer is removed
  3. extractionthe aqueous layer is extracted with dichloromethane
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate is concentrated under vacuum
  8. customThe resulting material is purified by silica gel column chromatography
  9. washeluting with ethyl acetate and hexane
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-258de73f335a4346a759561e37bc1201
Source dataset
uspto-grants-2014_03
Patent number
US08673928B2

Reaction notes

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