Water → 3-(2,2-Diethoxyethoxy)-5,6-difluoro-N-(2-fluoro-4-iodophenyl)-2-nitroaniline

HRID 1261394

Reaktionsgleichung

Reaktionsgleichung von HRID 1261394
[CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH2:5][OH:6])[CH3:2].[H-].[Na+].[F:12][C:13]1[C:27]([F:28])=[CH:26][C:25](F)=[C:24]([N+:30]([O-:32])=[O:31])[C:14]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([I:22])=[CH:18][C:17]=1[F:23].O>C1COCC1>[CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH2:5][O:6][C:25]1[C:24]([N+:30]([O-:32])=[O:31])=[C:14]([C:13]([F:12])=[C:27]([F:28])[CH:26]=1)[NH:15][C:16]1[CH:21]=[CH:20][C:19]([I:22])=[CH:18][C:17]=1[F:23])[CH3:2]

Komponenten

6

Edukt 4

HCID 962WaterHCID 121292,2-DiethoxyethanolHCID 24758Sodium hydrideHCID 574300722,3,5-trifluoro-N-(2-fluoro-4-iodophenyl)-6-nitroaniline2×

Produkt 1

HCID 866714883-(2,2-Diethoxyethoxy)-5,6-difluoro-N-(2-fluoro-4-iodophenyl)-2-nitroanilineAusbeute 54,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
2.5 °C

Versuchsvorschrift

For large scale synthesis, 2,2-diethoxyethanol was added dropwise into a suspension of 60% sodium hydride in 5 L of THF at 1-2° C. over 30 minutes and then stirred at 0-5° C. for 1.5 hours. A solution of 750 g of 2,3,5-trifluoro-N-(2-fluoro-4-iodophenyl)-6-nitroaniline in 2.25 L of THF was then added dropwise into the above suspension at 0-5° C. After the addition, the purple solution was stirred at room temperature for 2 days and 17 hours. HPLC analysis showed 4.1% remaining of 2,3,5-trifluoro-N-(2-fluoro-4-iodophenyl)-6-nitroaniline. 150 mL of water was added very slowly (gas generated) into the pre-cooled solution at 10° C. The solution was then concentrated to dryness. The resultant oil was then suspended in 5 L of heptanes and seeded with pure 3-(2,2-diethoxyethoxy)-5,6-difluoro-N-(2-fluoro-4-iodophenyl)-2-nitroaniline crystal and stirred for 30 minutes. After 1 hour of stirring, the precipitate was filtered and dried to yield 520 g (54.3%) of product with 96.4% purity. Further product was available in the mother liquor. 1H NMR (CDCl3, 400 MHz): δ 7.42 (dd, 1H), 7.34 (d, 1H), 6.87 (bs, 1H), 6.56-6.67 (m, 2H), 4.79 (t, 1H), 4.06 (d, 2H), 3.74-3.82 (m, 2H), 3.59-3.66 (m, 2H); 1.24 (t, 6H).

Aufarbeitung

  1. additionAfter the addition
  2. stirringthe purple solution was stirred at room temperature for 2 days and 17 hours
  3. concentrationThe solution was then concentrated to dryness
  4. stirringstirred for 30 minutes
  5. stirringAfter 1 hour of stirring
  6. filtrationthe precipitate was filtered
  7. customdried

Quellen und Nachweise

ORD-Eintrag
ord-b7b9a7c6bb0e437792a6f20603b4b3e2
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08470878B2

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