Sodium Hydroxide → HCID 17858942, compound

HRID 1372727Notes

Reaction equation

HRID 1372727 reaction equation
[F:1][C:2]1[C:7]2[C:8]([C:11]([OH:13])=O)=[N:9][S:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[NH2:14][C:15]1[C:20]([Cl:21])=[CH:19][C:18]([CH2:22][C:23]([O:25]CC)=[O:24])=[C:17]([F:28])[CH:16]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[OH-].[Na+]>CN(C=O)C.CN(C1C=CN=CC=1)C.Cl.C1COCC1>[Cl:21][C:20]1[C:15]([NH:14][C:11]([C:8]2[C:7]3[C:2]([F:1])=[CH:3][CH:4]=[CH:5][C:6]=3[S:10][N:9]=2)=[O:13])=[CH:16][C:17]([F:28])=[C:18]([CH2:22][C:23]([OH:25])=[O:24])[CH:19]=1

Participants

10

Reactant 5

HCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 17858807Ethyl 4-amino-5-chloro-2-fluorophenylacetateHCID 17859128HCID 17859128, compound

Product 1

HCID 17858942HCID 17858942, compoundYield 22.5%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 313Hydrochloric AcidSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

In DMF (10 ml) were dissolved 4-fluorobenzo(d)isothiazole-3-carboxylic acid (240 mg, 1.22 mmol), ethyl 4-amino-5-chloro-2-fluorophenylacetate (282 mg, 1.22 mmol), HOBt (313 mg, 2.32 mmol), EDC HCl (351 mg, 1.83 mmol) and DMAP (catalytic amount). The resulting solution was stirred for 4 days at room temperature. 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 chromatography system from Yamazen, chloroform, 8 ml/min, φ 15 mm×300 mm). To the resulting ester were added THF (12 ml) and 0.25M NaOH (7.32 ml, 1.83 mmol), followed by stirring at room temperature for 4 hours. The reaction mixture was poured in 1M HCl to acidify the mixture. 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-((4-fluoro-3-benzo(d)isothiazolylcarbonyl)amino)phenyl)acetic acid (105 mg, 22%) as a colorless solid.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationdistilled under reduced pressure
  5. customto remove the solvent
  6. customThe residue was purified by silica gel column chromatography (middle pressure chromatography system from Yamazen, chloroform, 8 ml/min, φ 15 mm×300 mm)
  7. stirringby stirring at room temperature for 4 hours
  8. customThe crystals thus precipitated
  9. filtrationwere collected by filtration under reduced pressure
  10. washwashed with water
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-7c6970f3adb64f6ab098d5ee11fb4a1c
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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