Hydrochloric Acid → HCID 10193630, compound

HRID 2181456Notes

Reaction equation

HRID 2181456 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([C:9]([NH:11][O:12][CH2:13][CH2:14][OH:15])=[O:10])[C:3]=1[NH:16][C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23]C)=[O:22])=[CH:19][CH:18]=1.[OH-].[Na+].Cl>C(O)C>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([C:9]([NH:11][O:12][CH2:13][CH2:14][OH:15])=[O:10])[C:3]=1[NH:16][C:17]1[CH:26]=[CH:25][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 10126224HCID 10126224, compound

Product 1

HCID 10193630HCID 10193630, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The product of Example 17, Step A, methyl 4-[[2,3-difluoro-6-[[(2-hydroxyethoxy)amino]carbonyl]phenyl]amino]benzoate (306 mg, 0.84 mmol) was dissolved in ethanol (40 mL), to which was added 1 M NaOH solution (40 mL). This mixture was stirred at room temperature for 15 hours, then poured into 1 M HCl solution (100 mL). The resulting precipitate was extracted with EtOAc (3×80 mL) and the combined EtOAc extracts then combined and washed with water (2×100 mL) and saturated NaCl (100 mL). The organic fraction was dried (Na2SO4), the solvent removed under reduced pressure and the resulting residue purified by column chromatography on flash silica (50% EtOAc/hexanes as eluant) to afford 4-[[2,3-difluoro-6-[[(2-hydroxyethoxy)amino]carbonyl]phenyl]-amino]benzoic acid as a crystalline white solid (168 mg, 57%); m.p. (EtOAc/hexanes) 180-183° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.89 (br s, 2 H), 8.75 (br s, 1 H), 7.75 (d, J=8.8 Hz, 2 H), 7.41-7.25 (m, 2 H), 6.79 (dd, J=8.6, 1.7 Hz, 2 H), 4.76 (br s, 1 H), 3.76 (t, J=4.8 Hz, 2 H), 3.50 (t, J=4.8 Hz, 2 H). Anal. Calcd for C16H14F2N2O5: C, 54.5; H, 4.0; N, 8.0. Found: C, 54.8; H, 3.9; N, 8.0. Step C: Preparation of 2,3,4,5,6-pentafluorophenyl 4-[[2,3-difluoro-6-[[(2-hydroxyethoxy)-amino]carbonyl]-phenyl]amino]benzoate

Workup

  1. extractionThe resulting precipitate was extracted with EtOAc (3×80 mL)
  2. washwashed with water (2×100 mL) and saturated NaCl (100 mL)
  3. dry with materialThe organic fraction was dried (Na2SO4)
  4. customthe solvent removed under reduced pressure
  5. customthe resulting residue purified by column chromatography on flash silica (50% EtOAc/hexanes as eluant)

Sources & evidence

ORD record
ord-fcaf36b05428452a80709da1c9fdaa91
Source dataset
uspto-grants-2005_05
Patent number
US06891066B2

Reaction notes

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