N-Methylisatoic anhydride → 2-Methylamino-benzoic acid 3-(2-dodecyloxy-5-methyl-phenylcarbamoyl)-4-hydroxy-naphthalen-1-yl ester

HRID 2214332Notes

Reaction equation

HRID 2214332 reaction equation
[CH3:1][N:2]1[C:8](=O)[O:7][C:5](=[O:6])[C:4]2=[CH:10][CH:11]=[CH:12][CH:13]=[C:3]12.C(N(CC)C(C)C)(C)C.[CH2:23]([O:35][C:36]1[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][C:37]=1[NH:43][C:44]([C:46]1[CH:55]=C(O)[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:47]=1[OH:57])=[O:45])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]>CCCCCC.O1CCCC1>[CH3:1][NH:2][C:3]1[CH:13]=[CH:12][CH:11]=[CH:10][C:4]=1[C:5]([O:7][C:8]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:47]([OH:57])=[C:46]([C:44](=[O:45])[NH:43][C:37]2[CH:38]=[C:39]([CH3:42])[CH:40]=[CH:41][C:36]=2[O:35][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH:55]=1)=[O:6]

Participants

6

Reactant 3

HCID 25160N-Methylisatoic anhydride2×HCID 81531DiisopropylethylamineHCID 23558027HCID 23558027, compound

Product 1

HCID 695897322-Methylamino-benzoic acid 3-(2-dodecyloxy-5-methyl-phenylcarbamoyl)-4-hydroxy-naphthalen-1-yl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

N-Methylisatoic anhydride (18.00 g, 90% technical grade containing mineral oil) was suspended in hexane (300 ml) and stirred for 0.75 hr at room temperature. The solid was filtered under suction, washed with petroleum ether (40–60° C.) and dried briefly before use. 1,4-Dihydroxy-naphthalene-2-carboxylic acid (2-dodecyloxy-5-methyl-phenyl)-amide was recrystallised from a mixture of petroleum ether (60–80° C.) and toluene before use. N,N-Diisopropylethylamine (16.20 g, 0.125 mol) was added to a stirred suspension of 1,4-dihydroxy-naphthalene-2-carboxylic acid (2-dodecyloxy-5-methyl-phenyl)-amide (29.14 g, 0.061 mol) and N-methylisatoic anhydride (12.00 g {of 90%}, 0.061 mol) in tetrahydrofuran (150 ml, dried over 4 Å molecular sieves) under an atmosphere of argon. The reaction was heated to reflux overnight. An aliquot was removed, added to dilute hydrochloric acid and extracted with ethyl acetate. Thin layer chromatography indicated the presence of a small amount of residual starting naphthol. A further quantity of N-methylisatoic anhydride (1.1 g) was added and the reflux continued for a further 18 hr. The reaction was allowed to cool and then the solvent was removed under reduced pressure. The residue was taken-up in a mixture of dilute aqueous (2 M) hydrochloric acid (500 ml) and warm ethyl acetate (1000 ml). Some material failed to dissolve and collected at the interface. The buff solid was filtered, washed with ethyl acetate and dried in vacuo (27.3 g). The organic solution was separated and dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Methanol (100 ml) was added and the mixture stirred and boiled under reflux for 15 min and then allowed to cool. A further quantity of a solid precipitated which was filtered and dried in vacuo (3.8 g). The solids were analysed and the results were consistent with the desired 2-methylamino-benzoic acid 3-(2-dodecyloxy-5-methylphenylcarbamoyl)-4-hydroxy-naphthalen-1-yl ester. The total yield of product was 31.1 g (83%).

Workup

  1. filtrationThe solid was filtered under suction
  2. washwashed with petroleum ether (40–60° C.)
  3. customdried briefly before use
  4. custom1,4-Dihydroxy-naphthalene-2-carboxylic acid (2-dodecyloxy-5-methyl-phenyl)-amide was recrystallised from a mixture of petroleum ether (60–80° C.) and toluene before use
  5. temperatureThe reaction was heated
  6. temperatureto reflux overnight
  7. customAn aliquot was removed
  8. additionadded to dilute hydrochloric acid
  9. extractionextracted with ethyl acetate
  10. additionA further quantity of N-methylisatoic anhydride (1.1 g) was added
  11. waitthe reflux continued for a further 18 hr
  12. temperatureto cool
  13. customthe solvent was removed under reduced pressure
  14. additionThe residue was taken-up in a mixture of dilute aqueous (2 M) hydrochloric acid (500 ml)
  15. temperaturewarm ethyl acetate (1000 ml)
  16. dissolutionto dissolve
  17. customcollected at the interface
  18. filtrationThe buff solid was filtered
  19. washwashed with ethyl acetate
  20. customdried in vacuo (27.3 g)
  21. customThe organic solution was separated
  22. dry with materialdried over anhydrous magnesium sulfate
  23. filtrationfiltered
  24. concentrationconcentrated under reduced pressure
  25. additionMethanol (100 ml) was added
  26. stirringthe mixture stirred
  27. temperatureunder reflux for 15 min
  28. temperatureto cool
  29. customA further quantity of a solid precipitated which
  30. filtrationwas filtered
  31. customdried in vacuo (3.8 g)

Sources & evidence

ORD record
ord-d908ba278893472e8df0a2d69d9bf2f8
Source dataset
uspto-grants-2006_09
Patent number
US07108964B2

Reaction notes

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