Hydrochloric Acid → N-cyclopentyl-N,2-dihydroxy-4-methoxybenzamide

HRID 404973

Reaktionsgleichung

Reaktionsgleichung von HRID 404973
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=[O:9])C.[CH3:11][O:12][C:13]1[CH:14]=[C:15]([OH:22])[C:16](=[CH:20][CH:21]=1)[C:17](O)=[O:18].Cl.C(Cl)(=O)C(Cl)=O.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl.O1CCCC1.O>[CH:6]1([N:1]([OH:9])[C:17](=[O:18])[C:16]2[CH:20]=[CH:21][C:13]([O:12][CH3:11])=[CH:14][C:15]=2[OH:22])[CH2:5][CH2:4][CH2:3][CH2:2]1

Komponenten

10

Edukt 6

HCID 313Hydrochloric Acid2×HCID 1049PyridineHCID 6367Acetyl chlorideHCID 10340Sodium CarbonateHCID 65578Oxalyl chlorideHCID 752314-Methoxysalicylic Acid

Produkt 1

HCID 50994754N-cyclopentyl-N,2-dihydroxy-4-methoxybenzamideAusbeute 79 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel3×HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Pyridine (2.05 mL, 25 mmol) and acetyl chloride (0.89 mL, 12.5 mmol were added to a solution of 4-methoxy salicylic acid (0.84 g, 5 mmol) in CH2Cl2 (20 mL) at 0° C. The reaction mixture was gradually warmed to room temperature over 30 min and then poured into water. The resulting biphasic mixture was further stirred for 1 h and then acidified with 1 N HCl and extracted with ethyl acetate. The crude acetoxy compound (assuming 100% conversion) obtained was then converted to the acid chloride by heating to reflux with oxalyl chloride (1.3 mL, 15 mmol) in CH2Cl2 (20 mL) for 1 h. After removal of the volatile materials, the acid chloride (1.05 g, 4.38 mmol) in CH2Cl2 (20 mL) was added to a stirred mixture of sodium carbonate (1N, 17.5 mL) and C5H9NH.OH (1.32 g, 13.2 mmol) in tetrahydrofuran (30 mL) at 0° C. The resulting mixture was stirred at room temperature for 1 h and then acidified with 0.5 M HCl and then extracted with ethyl acetate. The crude product was purified by column chromatography on silica using hexanes:ethyl acetate to afford N-cyclopentyl-N,2-dihydroxy-4-methoxybenzamide (1 g, 79%) as a colorless solid. 1H NMR (300 MHz, DMSO-d6): δ 7.88 (d, 1H, J=8.6 Hz), 6.92 (d, 1H, J=8.6 Hz), 6.82 (s, 1H), 3.80 (s, 3H), 3.79-3.70 (m, 1H), 1.69-1.63 (m, 2H), 1.55-1.52 (m, 6H). LC-MS (ESI) Calcd for C13H17NO4 [M+H]+: 252.12. Found: 252.00.

Aufarbeitung

  1. extractionextracted with ethyl acetate
  2. customThe crude acetoxy compound (assuming 100% conversion) obtained
  3. temperatureby heating
  4. customAfter removal of the volatile materials
  5. customat 0° C
  6. stirringThe resulting mixture was stirred at room temperature for 1 h
  7. extractionextracted with ethyl acetate
  8. customThe crude product was purified by column chromatography on silica

Quellen und Nachweise

ORD-Eintrag
ord-e3aa99f254d5405eb6573201cde7aafa
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08748632B2

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