Trimethyl orthoformate → 1-(3-cyclopropyl-2-fluoro-5-nitrophenyl)-1H-tetrazole

HRID 710215Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 710215
[CH:1]1([C:4]2[C:5]([F:14])=[C:6]([CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=2)[NH2:7])[CH2:3][CH2:2]1.C[Si]([N:19]=[N+:20]=[N-:21])(C)C.[CH3:22]OC(OC)OC.[OH-].[Na+]>CC(O)=O.CCOC(C)=O>[CH:1]1([C:4]2[C:5]([F:14])=[C:6]([N:7]3[CH:22]=[N:19][N:20]=[N:21]3)[CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=2)[CH2:3][CH2:2]1

Komponenten

7

Edukt 4

HCID 9005Trimethyl orthoformateHCID 14798Sodium HydroxideHCID 78378AzidotrimethylsilaneHCID 580658083-Cyclopropyl-2-fluoro-5-nitroaniline

Produkt 1

HCID 580657871-(3-cyclopropyl-2-fluoro-5-nitrophenyl)-1H-tetrazoleAusbeute 92,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A mixture of 3-cyclopropyl-2-fluoro-5-nitroaniline (1.27 g, 6.47 mmol, 1 equiv), trimethylsilyl azide (4.26 mL, 32.37 mmol, 5 equiv), trimethylorthoformate (7.09 mL, 67.74 mmol, 10 equiv) in AcOH (15 mL) was heated to 70° C. and stirred for 7 hours behind a blast shield. After allowing to cool to room temperature, the mixture was further cooled in ice-water and basified to ca. pH 12-14 with 1N NaOH and diluted with EtOAc. The aqueous and organic layers were partitioned and the aqueous extracted with EtOAc (2×200 mL). The combined organic extracts were washed with 1N NaOH (1×200 mL), dried (Na2SO4), filtered, and the solvent removed under vacuum—silica gel was added at this stage so that the crude product was absorbed directly on to silica gel. The crude product was purified by column chromatography on silica gel using EtOAc/hexanes (30-50% EtOAc in increments of 10% EtOAc) to give the product 1-(3-cyclopropyl-2-fluoro-5-nitrophenyl)-1H-tetrazole (1.49 g, 92%) as a light-yellow solid.

Aufarbeitung

  1. temperatureto cool to room temperature
  2. customThe aqueous and organic layers were partitioned
  3. extractionthe aqueous extracted with EtOAc (2×200 mL)
  4. washThe combined organic extracts were washed with 1N NaOH (1×200 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvent removed under vacuum—silica gel
  8. additionwas added at this stage so that the crude product
  9. customwas absorbed directly on to silica gel
  10. customThe crude product was purified by column chromatography on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-a833287ad9054064aed58497bdd586af
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09181222B2

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