Diisopropylethylamine → 5-ethyl-6-methoxy-2-methyl-nicotinic acid N'-formylhydrazide

HRID 1921350Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1921350
[CH2:1]([C:3]1[C:4]([O:13][CH3:14])=[N:5][C:6]([CH3:12])=[C:7]([CH:11]=1)[C:8]([OH:10])=O)[CH3:2].F[B-](F)(F)F.[O:20]=[C:21]1C=CC=C[N:22]1OC(N(C)C)=[N+](C)C.O.OC1C2N=N[NH:42]C=2C=CC=1.C(N(C(C)C)C(C)C)C>ClCCl.O>[CH:21]([NH:22][NH:42][C:8](=[O:10])[C:7]1[CH:11]=[C:3]([CH2:1][CH3:2])[C:4]([O:13][CH3:14])=[N:5][C:6]=1[CH3:12])=[O:20]

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733204O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 674920765-Ethyl-6-methoxy-2-methyl-nicotinic acidHCID 178526939HCID 178526939, Verbindung

Produkt 1

HCID 674921155-ethyl-6-methoxy-2-methyl-nicotinic acid N'-formylhydrazideAusbeute 59,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Under a nitrogen atmosphere in a round bottom flask, 5-ethyl-6-methoxy-2-methyl-nicotinic acid (500 mg, 2.56 mmol) is dissolved in dichloromethane (30 mL). O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (990 mg, 3.33 mmol) is added, followed by hydroxybenzotriazole hydrate (510 mg, 3.33 mmol). The resulting mixture is stirred at rt for 40 min to give a suspension, which is treated with formyl hydrazide (231 mg, 3.85 mmol) followed by N-ethyl-diisopropylamine (1.16 mL, 6.66 mmol) to give a solution. After stirring at rt for 23 hr, LC/MS shows the reaction to be incomplete. The reaction is allowed to stir for a further 97 hr at room temperature. The reaction is diluted with water and the mixture is extracted with six portions of dichloromethane, the combined extract is dried over magnesium sulfate, filtered and evaporated. The crude product is purified by flash chromatography on a 10-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (1:1, increasing to 1:2). Fractions containing the product are combined, and the product triturated with ether to give 5-ethyl-6-methoxy-2-methyl-nicotinic acid N′-formylhydrazide (361 mg) as a white solid that was used without further purification. MS: m/e=238 (M+H); 1H NMR (300 MHz, CDCl3, δ, ppm): 9.05 (1H, br.s), 8.71 (1H, br.s), 8.20 (1H, s), 7.49 (1H, s), 3.97 (3H, s), 2.58 (3H, s), 2.56 (2H, q), 1.16 (3H, t).

Aufarbeitung

  1. customto give a suspension, which
  2. customto give a solution
  3. stirringAfter stirring at rt for 23 hr
  4. customthe reaction
  5. stirringto stir for a further 97 hr at room temperature
  6. extractionthe mixture is extracted with six portions of dichloromethane
  7. extractionthe combined extract
  8. dry with materialis dried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product is purified by flash chromatography on a 10-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (1:1, increasing to 1:2)
  12. additionFractions containing the product
  13. customthe product triturated with ether

Quellen und Nachweise

ORD-Eintrag
ord-cf0f387c00eb4f7db17c99894f852ebf
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173682B2

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