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

HRID 710209

Reaktionsgleichung

Reaktionsgleichung von HRID 710209
[CH:1]1([C:4]2[C:10]([F:11])=[CH:9][C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:5]=2[NH2:6])[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:10]([F:11])=[CH:9][C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:5]=2[N:6]2[CH:22]=[N:19][N:20]=[N:21]2)[CH2:3][CH2:2]1

Komponenten

7

Edukt 4

HCID 9005Trimethyl orthoformateHCID 14798Sodium HydroxideHCID 78378AzidotrimethylsilaneHCID 580657992-Cyclopropyl-3-fluoro-5-nitroaniline

Produkt 1

HCID 580657881-(2-cyclopropyl-3-fluoro-5-nitrophenyl)-1H-tetrazoleAusbeute 90 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A mixture of 2-cyclopropyl-3-fluoro-5-nitroaniline (300 mg, 1.53 mmol, 1 equiv), trimethylsilyl azide (1.0 mL, 7.65 mmol, 5 equiv), trimethylorthoformate (1.67 mL, 15.29 mmol, 10 equiv) in AcOH (3 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 (2×150 mL). The combined organic extracts were washed with 1N NaOH (1×100 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-(2-cyclopropyl-3-fluoro-5-nitrophenyl)-1H-tetrazole (343 mg, 90%) as a white solid.

Aufarbeitung

  1. temperatureto cool to room temperature
  2. customThe aqueous and organic layers were partitioned
  3. extractionthe aqueous extracted with EtOAc (2×150 mL)
  4. washThe combined organic extracts were washed with 1N NaOH (1×100 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-4f49945e7d1941e89b2714058fa28e88
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09181222B2

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