Sodium Hydroxide → 2-Hydroxy-4-[2-({[1-phenylethylidene]amino}oxy)ethoxy]benzoic acid

HRID 29648

Reaction equation

HRID 29648 reaction equation
[C:1]1([C:7](=[N:9][OH:10])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[O:12][C:13](=[O:25])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22]Br)=[CH:16][C:15]=1[OH:24].[OH-].[Na+]>O1CCCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[OH:24][C:15]1[CH:16]=[C:17]([O:20][CH2:21][CH2:22][O:10][N:9]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH3:8])[CH:18]=[CH:19][C:14]=1[C:13]([OH:25])=[O:12]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 69185AcetophenonoximeHCID 574195214-(2-Bromo-ethoxy)-2-hydroxy-benzoic acid methyl ester

Product 1

HCID 860393012-Hydroxy-4-[2-({[1-phenylethylidene]amino}oxy)ethoxy]benzoic acidYield 27%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-phenyl-ethanone oxime (1.156 g, 8.55 mmol) in tetrahydrofuran (75 mL) was added 4-(2-bromo-ethoxy)-2-hydroxy-benzoic acid methyl ester (2.346 g, 8.52 mmol), tetrabutylammonium iodide (0.968 g, 2.62 mmol) and 15% sodium hydroxide solution (30 mL). The reaction was heated at reflux overnight, cooled to room temperature and the layers were separated. The aqueous layer was neutralized to pH 7 by the addition of concentrated hydrochloric acid and extracted with ethyl acetate. The combined organics were washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography using ethyl acetate/hexanes (25/75)+1% formic acid to afford 2-hydroxy-4-[2-(1-phenyl-ethylideneaminooxy)-ethoxy]-benzoic acid (0.712 g, 27%) as a white solid. mp=149.1-150.4° C.; mass spectrum (+APCI, M+H) m/z 316. 1H NMR (400 MHz, DMSO-d6); δ 13.60 (bs, 1H), 11.50 (bs, 1H), 7.66 (m, 3H), 7.39 (m, 3H), 6.53 (m, 2H), 4.44 (t, 2H), 4.31 (t, 2H), 2.17 (s, 3H). Elemental analysis: Calcd. for C17H17NO5: C, 67.7; H, 5.43; N, 4.44, Found: C, 64.45; H, 5.32; N, 4.42.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux overnight
  3. customthe layers were separated
  4. additionThe aqueous layer was neutralized to pH 7 by the addition of concentrated hydrochloric acid
  5. extractionextracted with ethyl acetate
  6. washThe combined organics were washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-6fdbcbd94e574cbe9609207ad1def98e
Source dataset
uspto-grants-2008_09
Patent number
US07420083B2

Linked notes

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