Hydrochloric Acid → 2-(4,5-Difluoro-2-nitro-phenylamino)-5-methyl-thiophene-3-carbonitrile

HRID 131382

Reaktionsgleichung

Reaktionsgleichung von HRID 131382
[H-].[Na+].[NH2:3][C:4]1[S:5][C:6]([CH3:11])=[CH:7][C:8]=1[C:9]#[N:10].[F:12][C:13]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[C:16](F)=[CH:15][C:14]=1[F:23].Cl>C1COCC1>[F:12][C:13]1[C:14]([F:23])=[CH:15][C:16]([NH:3][C:4]2[S:5][C:6]([CH3:11])=[CH:7][C:8]=2[C:9]#[N:10])=[C:17]([N+:19]([O-:21])=[O:20])[CH:18]=1

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 750121,2,4-Trifluoro-5-nitrobenzeneHCID 6890562-Amino-5-methyl-3-thiophenecarbonitrile

Produkt 1

HCID 586260262-(4,5-Difluoro-2-nitro-phenylamino)-5-methyl-thiophene-3-carbonitrileAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
2.5 °C

Versuchsvorschrift

Add sodium hydride, 60% dispersion in mineral oil (55.0 g×60%=33.0 g, 1.38 mol) to THF (950 mL) with stirring at 0-5° C. under nitrogen. Add a solution of 2-amino-5-methyl-thiophene-3-carbonitrile (95.0 g, 0.687 mol) and 1,2,4-trifluoro-5-nitro-benzene (121.7 g, 0.687 mol) in THF (1325 mL) dropwise over ˜1 hour, keeping the temperature below 10° C. Allow the reaction to warm to ambient temperature and stir for 8-20 hours. Cool to 10-15° C. and add aqueous 1N HCl (550 mL) dropwise over 10-15 minutes to adjust the pH to 7.0-7.2, keeping the pot temperature below 15° C. Remove most of the organic portion under reduced pressure, and then filter and rinse with water. Dry at 50-60° C. to obtain the crude product. Purify by flash chromatography, eluting with 1:1/methylene chloride:heptane to give 89.1 g (44%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 9.77 (bs, 1H), 8.33 (m, 1H), 7.09 (s, 1H), 7.07 (m, 1H), 2.47 (s, 3H). HRMS (ES) exact mass M+H calcd for C12H7F2N3O2S 318.0125; found 318.0133.

Aufarbeitung

  1. customthe temperature below 10° C
  2. customthe reaction
  3. temperatureto warm to ambient temperature
  4. stirringstir for 8-20 hours
  5. temperatureCool to 10-15° C.
  6. customthe pot temperature below 15° C
  7. customRemove most of the organic portion under reduced pressure
  8. filtrationfilter
  9. washrinse with water
  10. customDry at 50-60° C.
  11. customto obtain the crude product
  12. customPurify by flash chromatography
  13. washeluting with 1:1/methylene chloride

Quellen und Nachweise

ORD-Eintrag
ord-22035220efcd4a1abca94f3b63973c9f
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07384934B2

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