Carbamate → 2-(3,5-Bis-trifluoromethyl-benzoylamino)-4-nitro-benzoic acid methyl ester

HRID 29667

Reaktionsgleichung

Reaktionsgleichung von HRID 29667
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:5]=1[NH2:13].C(N(CC)CC)C.[F:22][C:23]([F:38])([F:37])[C:24]1[CH:25]=[C:26]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[C:27](Cl)=[O:28].C(=O)([O-])N>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:5]=1[NH:13][C:27](=[O:28])[C:26]1[CH:30]=[C:31]([C:33]([F:34])([F:35])[F:36])[CH:32]=[C:24]([C:23]([F:22])([F:37])[F:38])[CH:25]=1

Komponenten

6

Edukt 4

HCID 276CarbamateHCID 8471Triethylamine2×HCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 596476Methyl 4-nitroanthranilate

Produkt 1

HCID 865973982-(3,5-Bis-trifluoromethyl-benzoylamino)-4-nitro-benzoic acid methyl esterAusbeute 33,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 2-amino-4-nitro-benzoic acid methyl ester (5.00 g, 25.5 mmol) in methylene chloride (75 mL) was added triethylamine (4.13 g, 40.8 mmol) followed by 3,5-bis-trifluoromethyl-benzoyl chloride (8.46 g, 30.6 mmol). This mixture was allowed to stir overnight at ambient temperature. Work-up of an aliquot of the reaction mixture revealed incomplete reaction. Additional 0.5 equivalents of the acid chloride (2.3 mL) and triethylamine (1.8 mL) were added and the mixture was refluxed overnight. The reaction mixture was allowed to cool and filtered. The filtrate was partitioned against brine, the layers were separated, and the aqueous layer was extracted with one portion of ethyl acetate. The organics were combined, dried over MgSO4, filtered and concentrated under reduced pressure. The resultant paste was dissolved in methylene chloride (25 mL) and the product was precipitated out by the addition of hexanes (175 mL). The precipitate was isolated by filtration and determined to be a mixture of the desired amide (mono-acylated) product and the carbamate (di-acylated) side product. The crude material was purified by flash chromatography through silica gel using ethyl acetate/hexanes (15/85 gradient to 30/70) to give 2-(3,5-bis-trifluoromethyl-benzoylamino)-4-nitro-benzoic acid methyl ester (3.7 g, 33%) as an off-white solid. 1H NMR (400 MHz, CDCl3); δ 12.40 (bs, 1H), 9.78 (d, 1H), 8.50 (s, 2H), 8.31 (d, 1H), 8.11 (s, 1H), 8.00 (dd, 1H), 4.07 (s, 3H). 1H NMR (400 MHz, DMSO-d6); δ 9.04 (d, 1H), 8.43 (dd, 1H), 8.34 (s, 4H), 8.24 (s, 1H), 8.22 (s, 2H), 3.87 (s, 3H).

Aufarbeitung

  1. customreaction
  2. temperaturethe mixture was refluxed overnight
  3. temperatureto cool
  4. filtrationfiltered
  5. customThe filtrate was partitioned against brine
  6. customthe layers were separated
  7. extractionthe aqueous layer was extracted with one portion of ethyl acetate
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. dissolutionThe resultant paste was dissolved in methylene chloride (25 mL)
  12. customthe product was precipitated out by the addition of hexanes (175 mL)
  13. customThe precipitate was isolated by filtration
  14. customThe crude material was purified by flash chromatography through silica gel

Quellen und Nachweise

ORD-Eintrag
ord-e1d0ec6302c84750b7d753f2142f461a
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07420083B2

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