Hydrochloric Acid → 2-chloro-5,6-difluoro-1H-benzimidazole

HRID 9581

반응식

HRID 9581 반응식
N(OC(C)(C)C)=O.[F:8][C:9]1[C:18]([F:19])=[CH:17][C:12]2[NH:13][C:14](N)=[N:15][C:11]=2[CH:10]=1.[ClH:20]>CC(C)=O.[Cu](Cl)Cl>[Cl:20][C:14]1[NH:13][C:12]2[CH:17]=[C:18]([F:19])[C:9]([F:8])=[CH:10][C:11]=2[N:15]=1

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitrite2회HCID 106787085,6-difluoro-1H-1,3-benzodiazol-2-amine

생성물 1

HCID 4694162-chloro-5,6-difluoro-1H-benzimidazole수율 73%

시약·촉매·용매 2

HCID 24014Cupric Chloride촉매HCID 180Acetone용매

실험 절차

The procedure used was similar to that reported in J. Med. Chem. 40:811–818, 1997. To a mixture of copper(II) chloride (795 mg, 5.91 mmol) in acetone (20 mL) was added tert-butyl nitrite (0.53 mL, 4.43 mmol). The reaction mixture was stirred at rt for 20 minutes, 5,6-difluoro-1H-benzimidazol-2-amine (500 mg, 2.96 mmol) was then added, and the mixture was heated at reflux for 2 h (with additional portions of tert-butyl nitrite added every 0.5 h). The reaction mixture was then cooled to rt, treated with 2 N HCl, and extracted with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated in vacuo to afford 2-chloro-5,6-difluoro-1H-benzimidazole (580 mg, 73%), which was used without further purification in the next step. LC-MS m/z 189.2 (MH+), ret. time 1.96 min; 1H NMR (300 MHz, DMSO-d6) δ 7.62 (t, 2H), 13.5 (br s, 1H).

후처리

  1. temperaturethe mixture was heated
  2. additionadded every 0.5 h)
  3. temperatureThe reaction mixture was then cooled to rt
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-0467d96bb5b948119f036634bf79f67c
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07091228B2

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