Hydrochloric Acid → HCID 10193630, compound

HRID 1835652Notes

Reaction equation

HRID 1835652 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 1, 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 NaCI (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%); mp (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.

Workup

  1. extractionThe resulting precipitate was extracted with EtOAc (3×80 mL)
  2. washwashed with water (2×100 mL) and saturated NaCI (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-ba30fd6b0961411f83f96cae35c7dba2
Source dataset
uspto-grants-2004_08
Patent number
US06770778B2

Reaction notes

Loading…