Ethyl Bromide → 3-Ethyl-5-[1-(2-fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one

HRID 515418노트

반응식

HRID 515418 반응식
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[O:21][C:20](=[O:22])[NH:19][N:18]=2)[CH2:13][CH2:12]1.[CH2:23](Br)[CH3:24].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:23]([N:19]1[N:18]=[C:17]([CH:14]2[CH2:15][CH2:16][N:11]([C:3]3[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=3[F:1])[CH2:12][CH2:13]2)[O:21][C:20]1=[O:22])[CH3:24]

참가 물질

5

반응물 3

HCID 6332Ethyl BromideHCID 11430Potassium CarbonateHCID 896509215-[1-(2-Fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one

생성물 1

HCID 896511653-Ethyl-5-[1-(2-fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one수율 95%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

5-[1-(2-Fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5b, 1.23 g, 4 mmol) on reacting with C2H5Br (0.53 g, 4.8 mmol) in DMF in the presence of base K2CO3 (1.38 g, 10 mmol) at room temperature (27° C.) for 10 h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 3-ethyl-5-[1-(2-fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6e, 1.27 g, 95%). Nitro compound (6e, 1.34 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65° C. for 4 h, after completion of reaction methanol is evaporated under vacuum and to this saturated sodium bicarbonate solution, is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-amino-2-fluorophenyl)-4-piperidyl]-3-ethyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7 g, 1.05 g, 86%). To a stirred solution of 5-nitro2-furanoic acid in DMF add HOBT (Hydroxybenzo triazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl)carbodi imide)) (0.19 g, 1 mmol) and amine compound (7g, 0.3 g, 1 mmol) and stirred for 2 h at room temperature (27° C.), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-4-[4-(4-ethyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidino]-3-fluorophenyl-5-nitro-2-furamide (8 g, 391 mg, 88%).

후처리

  1. custom(27° C.)
  2. customfor 10 h
  3. customafter completion of the reaction, reaction mixture
  4. extractionextracted into chloroform finally purification by column chromatography

출처 및 근거

ORD 기록
ord-2d62e11e244149938cbd8c04fffcbf24
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108960B2

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