Hydrochloric Acid → 2-(4-Chloro-phenyl)-1-[1-cyclohexyl-2-(2-fluoro-phenoxy)-ethyl]-5,6-difluoro-1H-benzoimidazole

HRID 417084노트

반응식

HRID 417084 반응식
CN(C)[CH:3]=[O:4].[H-].[Na+].Br[CH2:9][CH:10]([N:17]1[C:21]2[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:20]=2[N:19]=[C:18]1[C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=1)[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.Cl>C(OCC)(=O)C>[Cl:34][C:31]1[CH:30]=[CH:29][C:28]([C:18]2[N:17]([CH:10]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)[CH2:9][O:4][C:3]3[CH:20]=[CH:21][CH:22]=[CH:23][C:24]=3[F:26])[C:21]3[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:20]=3[N:19]=2)=[CH:33][CH:32]=1

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 666193191-(2-bromo-1-cyclohexyl-ethyl)-2-(4-chloro-phenyl)-5,6-difluoro-1H-benzoimidazole

생성물 1

HCID 461844412-(4-Chloro-phenyl)-1-[1-cyclohexyl-2-(2-fluoro-phenoxy)-ethyl]-5,6-difluoro-1H-benzoimidazole수율 9%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 27 mg (0.24 mmol) 2-fluorophenole in 2 mL N,N-dimethylformamide 11 mg (0.24 mmol, 55% dispersion in mineral oil) sodium hydride were added and the reaction mixture stirred for 10 min. at room temperature. To the suspension 100 mg (0.22 mmol) 1-(2-bromo-1-cyclohexyl-ethyl)-2-(4-chloro-phenyl)-5,6-difluoro-1H-benzoimidazole were added. The reaction mixture was stirred for 18 h at room temperature, and then poured on 30 mL 1N hydrochloric acid and 30 mL ethyl acetate. The phases were separated and the aqueous layer extracted a second time with 30 mL ethyl acetate. The combined organic layers were washed twice with 30 mL water and once with 30 mL brine, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate 100:0 to 70:30) to give the desired compound as white solid (9%). MS (Turbo Spray): m/z=485.3 [M+H].

후처리

  1. stirringThe reaction mixture was stirred for 18 h at room temperature
  2. customThe phases were separated
  3. extractionthe aqueous layer extracted a second time with 30 mL ethyl acetate
  4. washThe combined organic layers were washed twice with 30 mL water and once with 30 mL brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with a gradient of n-heptane:ethyl acetate 100:0 to 70:30)

출처 및 근거

ORD 기록
ord-3985bf2656e74f869f6ce1d6b64e03ec
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08088930B2

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