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

HRID 417226

反応式

HRID 417226 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
50 °C

実験手順

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%).

後処理

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

出典と根拠

ORDレコード
ord-1a524774307d45fa97ae122e6351b988
出典データセット
uspto-grants-2012_01
特許番号
US08088815B2

関連ノート

読み込み中…