Isatoic Anhydride → 2-Amino-N-methoxybenzamide

HRID 1045915Notes

Reaction equation

HRID 1045915 reaction equation
Cl.[CH3:2][O:3][NH2:4].[NH:5]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[C:8](=O)[O:7]C1=O.CCN(C(C)C)C(C)C>C1COCC1>[NH2:5][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[C:8]([NH:4][O:3][CH3:2])=[O:7]

Participants

5

Reactant 3

HCID 8359Isatoic AnhydrideHCID 81531DiisopropylethylamineHCID 521874O-Methylhydroxylamine hydrochloride

Product 1

HCID 123927072-Amino-N-methoxybenzamideYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

O-Methylhydroxylamine hydrochloride (1.253 g, 15.00 mmol) was added to 1H-3,1-benzoxazine-2,4-dione (isatoic anhydride) (1.631 g, 10 mmol) in THF (50 mL) containing DIPEA (2.79 ml, 16.00 mmol). The resulting solution was stirred at room temperature for 4 hours and then heated to reflux for 17 hours. The mixture was allowed to cool to room temperature, filtered and then evaporated. The residue was dissolved in MeOH (20 mL) and then loaded onto an SCX column. The mixture was eluted first with MeOH and then with a 7N solution of NH3 in MeOH. Fractions containing product were combined and then evaporated to afford 2-amino-N-methoxybenzamide (1.410 g, 85% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 3.67 (3H, s), 6.26 (2H, s), 6.48 (1H, m), 6.70 (1H, dd), 7.15 (1H, m), 7.31 (1H, dd), 11.36 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+=167.41.

Workup

  1. temperatureheated
  2. temperatureto reflux for 17 hours
  3. temperatureto cool to room temperature
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe residue was dissolved in MeOH (20 mL)
  7. washThe mixture was eluted first with MeOH
  8. additionFractions containing product
  9. customevaporated

Sources & evidence

ORD record
ord-d8c4b2de77a24a538967360cbb325332
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Reaction notes

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