Pyridine → 3-[4-Hydroxy-2-(hydroxyimino-methyl)-phenyl]-acrylic acid tert-butyl ester

HRID 1181038Notes

Reaction equation

HRID 1181038 reaction equation
Cl.[NH2:2][OH:3].N1C=CC=CC=1.[C:10]([O:14][C:15](=[O:27])[CH:16]=[CH:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][C:19]=1[CH:25]=O)([CH3:13])([CH3:12])[CH3:11]>C(O)C>[C:10]([O:14][C:15](=[O:27])[CH:16]=[CH:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][C:19]=1[CH:25]=[N:2][OH:3])([CH3:13])([CH3:12])[CH3:11]

Participants

5

Reactant 3

HCID 1049PyridineHCID 443297Hydroxyamine hydrochlorideHCID 724795753-(2-Formyl-4-hydroxyphenyl)acrylic acid tert-butyl ester

Product 1

HCID 724795743-[4-Hydroxy-2-(hydroxyimino-methyl)-phenyl]-acrylic acid tert-butyl esterYield 101.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A slurry of hydroxylamine hydrochloride (8.33 g, 0.12 mol), pyridine (9.49 g, 0.12 mol), and ethanol (100 mL) was stirred at ambient temperature for 30 min. 3-(2-Formyl-4-hydroxy-phenyl)-acrylic acid tert-butyl ester (14.90 g, 0.06 mol) was added followed by an ethanol (49 mL) rinse. The resulting brown solution was stirred at ambient temperature for 16 h and concentrated. The residue was suspended in water (150 mL) and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with saturated NaCl solution (2×100 mL), dried (Na2SO4), and filtered through a plug of silica gel to remove trace polar impurities. The filtrate was concentrated to give crude product (16.04 g). A 13.56 g sample of the crude material was crystallized from heptane (70 mL) and ethyl acetate (80 mL) to the title compound (7.41 g, 55%), mp 146-149° C. 1H NMR (CD3OD): δ 1.53 (s, 9H), 4.83 (s, 2H), 6.15-6.23 (d, 1H), 6.82-6.87 (dd, 1H), 7.10-7.12 (d, 1H), 7.52-7.55 (d, 1H), 7.98-8.03 (d, 1H), 8.37 (s, 1H). MS (ES+) m/z 286.1 ([M+Na]+). MS (ES−) m/z 262.2 ([M−H]−). Anal. Calculated for C14H17NO4: C: 63.8658; H: 6.5081; N: 5.3198. Found: C: 63.71; H: 6.38; N: 5.51.

Workup

  1. washrinse
  2. concentrationconcentrated
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. washThe combined organic layers were washed with saturated NaCl solution (2×100 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered through a plug of silica gel
  7. customto remove trace polar impurities
  8. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-fb0c0591a7e34b6c92b992713a1fae37
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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