Piperidine → Z-6-chloro-3-(3-chloro-2-fluoro-benzylidene)-4-fluoro-1,3-dihydro-indol-2-one

HRID 417226

반응식

HRID 417226 반응식
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[C:4]([F:12])[CH:3]=1.[Cl:13][C:14]1[C:15]([F:22])=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH:17]=O.N1CCCCC1>CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5](/[C:6](=[CH:17]/[C:16]3[CH:19]=[CH:20][CH:21]=[C:14]([Cl:13])[C:15]=3[F:22])/[C:7](=[O:11])[NH:8]2)=[C:4]([F:12])[CH:3]=1

참가 물질

5

반응물 3

HCID 8082PiperidineHCID 7363353-Chloro-2-fluorobenzaldehydeHCID 666342786-Chloro-4-fluoroindolin-2-one

생성물 1

HCID 86653935Z-6-chloro-3-(3-chloro-2-fluoro-benzylidene)-4-fluoro-1,3-dihydro-indol-2-one수율 74.8%

시약·촉매·용매 1

HCID 887Methanol용매

반응 조건

온도
50 °C

실험 절차

To the mixture of 6-chloro-4-fluoroindolin-2-one (Natrochem, 85% purity) (1.1 g, 5.0 mmol) and 3-chloro-2-fluorobenzaldehyde (2.4 g, 15 mmol) (Oakwood) in methanol (50 mL) was added piperidine (1.7 g, 20 mmol) (Aldrich) dropwise. The mixture was then heated at 50° C. for 3 h. After cooled to 4° C., the mixture was filtered and resulting precipitate was collected, washed with cold methanol, dried to give the first batch of desired product (1.22 g). The filtrate was concentrated, and the residue was partitioned between ethyl acetate and water. The organic layer was separated, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (20-35% EtOAc in hexanes) to give the second batch of desired product (0.32 g). The two batches were combined to give E/Z-6-chloro-3-(3-chloro-2-fluoro-benzylidene)-4-fluoro-1,3-dihydro-indol-2-one as a yellow solid (Yield 1.54 g, 94%).

후처리

  1. temperatureAfter cooled to 4° C.
  2. filtrationthe mixture was filtered
  3. customresulting precipitate
  4. customwas collected
  5. washwashed with cold methanol
  6. customdried

출처 및 근거

ORD 기록
ord-1a524774307d45fa97ae122e6351b988
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08088815B2

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