Sodium hydride → 4-{2-[1-(4-Tert-butyl-phenyl)-ethylideneaminooxy]-ethoxy}-2-hydroxy-benzoic acid methyl ester

HRID 29646Notes

Reaction equation

HRID 29646 reaction equation
[H-].[Na+].[C:3]([C:7]1[CH:12]=[CH:11][C:10]([C:13](=[N:15][OH:16])[CH3:14])=[CH:9][CH:8]=1)([CH3:6])([CH3:5])[CH3:4].[CH3:17][O:18][C:19](=[O:31])[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28]Br)=[CH:22][C:21]=1[OH:30]>O1CCCC1>[CH3:17][O:18][C:19](=[O:31])[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][O:16][N:15]=[C:13]([C:10]2[CH:11]=[CH:12][C:7]([C:3]([CH3:6])([CH3:4])[CH3:5])=[CH:8][CH:9]=2)[CH3:14])=[CH:22][C:21]=1[OH:30]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 842752Ethanone, 1-[4-(1,1-dimethylethyl)phenyl]-, oximeHCID 574195214-(2-Bromo-ethoxy)-2-hydroxy-benzoic acid methyl ester

Product 1

HCID 865973834-{2-[1-(4-Tert-butyl-phenyl)-ethylideneaminooxy]-ethoxy}-2-hydroxy-benzoic acid methyl esterYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a slurry of sodium hydride (95%) (0.487 g, 20.3 mmol) in tetrahydrofuran (6 mL) was added 1-(4-tert-butyl-phenyl)-ethanone oxime (0.7021 g, 3.67 mmol) as a solution in tetrahydrofuran (18 mL) and the solution was allowed to stir at room temperature for 40 minutes. 4-(2-Bromo-ethoxy)-2-hydroxy-benzoic acid methyl ester (0.908 g, 3.64 mmol) was added as a solution in tetrahydrofuran (10 mL). The reaction was stirred at room temperature 1 hour and then heated at reflux 3 days. The reaction was cooled, quenched with brine 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 (5/95 to 10/90) afford 4-{2-[1-(4-tert-butyl-phenyl)-ethylideneaminooxy]-ethoxy}-2-hydroxy-benzoic acid methyl ester (0.546 g, 39%) as a yellow oil which solidified on standing. mp=65.4-66.8° C.; mass spectrum (+ESI, M+H) m/z 386. 1H NMR (400 MHz, DMSO-d6); δ 10.63 (s, 1H), 7.69 (d, 1H), 7.57 (d, 2H), 7.40 (d, 2H), 6.55 (m, 2H), 4.42 (t, 2H), 4.31 (t, 2H), 3.75 (s, 3H), 2.14 (s, 3H), 1.28 (s, 9H). Elemental analysis: Calcd. for C22H27NO5: C, 68.55; H, 7.06; N, 3.63, Found: C, 68.91; H, 7.10; N, 3.60.

Workup

  1. stirringThe reaction was stirred at room temperature 1 hour
  2. temperatureheated
  3. temperatureat reflux 3 days
  4. temperatureThe reaction was cooled
  5. customquenched with brine
  6. extractionextracted with ethyl acetate
  7. washThe combined organics were washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-c1a55d15133943bab290e508a602ed82
Source dataset
uspto-grants-2008_09
Patent number
US07420083B2

Reaction notes

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