Sodium Hydroxide → HCID 17859435, compound

HRID 1372729Notes

Reaction equation

HRID 1372729 reaction equation
[Cl:1][C:2]1[C:3]([NH:15][C:16]([C:18]2[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[S:20][N:19]=2)=[O:17])=[CH:4][C:5]([F:14])=[C:6]([CH2:8][C:9]([O:11]CC)=[O:10])[CH:7]=1.[OH-].[Na+]>C1COCC1.CO>[Cl:1][C:2]1[C:3]([NH:15][C:16]([C:18]2[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[S:20][N:19]=2)=[O:17])=[CH:4][C:5]([F:14])=[C:6]([CH2:8][C:9]([OH:11])=[O:10])[CH:7]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86592800HCID 86592800, compound

Product 1

HCID 17859435HCID 17859435, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

Methyl 4-amino-5-chloro-2-fluorophenylacetate (753 mg, 3.25 mmol), benzo(d)isothiazole-3-carboxylic acid (583 mg, 3.25 mmol), HOBt (834 mg, 6.18 mmol), EDC HCl (934 mg, 4.88 mmol) and DMAP (catalytic amount) were dissolved in DMF (16 ml). The resulting solution was stirred for 10 hours at 80° C. After cooling, the reaction mixture was poured in 1M HCl, followed by extraction with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (middle pressure, n-hexane/ethyl acetate 9:1, 15 ml/min, φ 50×300 mm) to give ethyl (5-chloro-2-fluoro-4-((3-benzo(d)isothiazolylcarbonyl)amino)phenyl)acetate. The resulting ester was dissolved in THF/methanol (4 ml, 3:1), and to the resulting solution was added 1M NaOH (1 ml). The mixture was stirred for 18 hours at room temperature. The solvent was distilled off under reduced pressure, and the residue was poured in 1M HCl. The crystals thus precipitated were collected by filtration under reduced pressure, washed with water and dried under reduced pressure to give (5-chloro-2-fluoro-4-((3-benzo(d)isothiazolylcarbonyl)amino)phenyl)acetic acid (354 mg, 30%) as a colorless solid.

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. additionthe residue was poured in 1M HCl
  3. customThe crystals thus precipitated
  4. filtrationwere collected by filtration under reduced pressure
  5. washwashed with water
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-13f0f30b83964a6ebb9a41661c6a959a
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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