Benzaldehyde → (2'R,3S)-5-chloro-2'-phenylspiro[indoline-3,3'-pyrrolidine]

HRID 529099노트

반응식

HRID 529099 반응식
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH2:13].[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.B(Cl)([C@H]1[C@H](C)[C@@H]2C(C)(C)[C@@H](C2)C1)[C@H]1[C@H](C)[C@@H]2C(C)(C)[C@@H](C2)C1.[OH-].[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]2[C@@:5]3([CH2:11][CH2:12][NH:13][C@@H:14]3[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:6][NH:7][C:8]2=[CH:9][CH:10]=1

참가 물질

6

반응물 4

HCID 240BenzaldehydeHCID 14798Sodium HydroxideHCID 773795-ChlorotryptamineHCID 11131038Chlorobis((1R,2S,3R,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)borane

생성물 1

HCID 68734286(2'R,3S)-5-chloro-2'-phenylspiro[indoline-3,3'-pyrrolidine]수율 35%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 2-(5-chloro-1H-indol-3-yl)ethanamine (1.67 g, 8.58 mmol) in DCM (43 mL) was added benzaldehyde (0.96 g, 9.0 mmol). The reaction mixture was stirred over molecular sieves 4 Å (4.1 g) overnight. The mixture was filtered through Celite. The filtrate was concentrated in vacuo. The crude product was dissolved in DCM (35 mL). A solution of (−)-Ipc2BCl (12.3 g, 38.2 mmol) in DCM (40 mL) was added to the reaction mixture. The resulting solution was stirred at about room temperature for about 3 days. Aqueous 15% NaOH solution (50 mL) was added and the mixture was stirred for about 15 min. The organic layer was separated. The aqueous layer was extracted with DCM. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by column chromatography (hexane:EtOAc, 1:1) to give the less polar product (2′R,3S)-5-chloro-2′-phenylspiro[indoline-3,3′-pyrrolidine] (0.73 g, 35%). Further elution with EtOAc gave the other diastereomer (2′S,3S)-5-chloro-2′-phenylspiro[indoline-3,3′-pyrrolidine] (0.50 g, 24%). LCMS (APCI+) m/z 285, 287 [M+H]+; Rt=2.35 min.

후처리

  1. filtrationThe mixture was filtered through Celite
  2. concentrationThe filtrate was concentrated in vacuo
  3. dissolutionThe crude product was dissolved in DCM (35 mL)
  4. stirringThe resulting solution was stirred at about room temperature for about 3 days
  5. stirringthe mixture was stirred for about 15 min
  6. customThe organic layer was separated
  7. extractionThe aqueous layer was extracted with DCM
  8. washThe combined organic layers were washed with brine
  9. customdried
  10. concentrationconcentrated
  11. customThe residue was purified by column chromatography (hexane:EtOAc, 1:1)

출처 및 근거

ORD 기록
ord-161e49d8e87045169821178c70cbdd6d
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346805B2

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