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

HRID 2190036Notes

Reaction equation

HRID 2190036 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 6344DichloromethaneSolvent3×

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. additionwas added to the reaction mixture
  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-5250b23967f34956b955358c410dd89f
Source dataset
uspto-grants-2012_12
Patent number
US08324221B2

Reaction notes

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