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

HRID 2370953

반응식

HRID 2370953 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 176Acetic Acid용매HCID 8857Ethyl Acetate용매

반응 조건

온도
70 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-94242536a4be4e3396df01528947aefb
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08710223B2

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