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

HRID 529099Notes

Reaction equation

HRID 529099 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-161e49d8e87045169821178c70cbdd6d
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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