Cesium carbonate → 1-(1H-indol-6-yl)pyrrolidin-3-ol

HRID 2361309Notes

Reaction equation

HRID 2361309 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[NH:11]1[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12]1.C(=O)([O-])[O-].[Cs+].[Cs+].N1CCC[C@H]1C(O)=O>CS(C)=O.[Cu]I>[NH:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([N:11]3[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12]3)[CH:10]=2)[CH:6]=[CH:7]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 982104-HydroxypyrrolidineHCID 145742L-ProlineHCID 6764936-Bromoindole

Product 1

HCID 679949181-(1H-indol-6-yl)pyrrolidin-3-olYield 50.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
95 °C

Procedure

To a pressure tube containing a light orange, homogeneous solution of 6-bromo-1H-indole (1.01 g, 5.15 mmol) in DMSO (8.58 mL) purged with nitrogen were added pyrrolidin-3-ol (4.49 g, 51.5 mmol), cesium carbonate (3.36 g, 10.30 mmol), copper(I) iodide (0.098 g, 0.515 mmol) and (S)-pyrrolidine-2-carboxylic acid (0.652 g, 5.67 mmol). The pressure tube was sealed and stirred at 95° C. for 5.5 hr. The reaction was cooled to room temperature and immersed in an ice-water bath. Ice water (20 mL) was added, and the mixture was stirred for 10 min. It was extracted with EtOAc (4×75 mL), and the organic layers were combined, dried over MgSO4, and concentrated in vacuo to give a residue which was purified by flash chromatography using an ISCO 120 g column eluting with 20-100% EtOAc/hexanes. Appropriate fractions were collected and concentrated in vacuo to give the desired product (0.5215 g, 2.58 mmol, 50.1% yield) as an off-white solid.

Workup

  1. custompurged with nitrogen
  2. customThe pressure tube was sealed
  3. temperatureThe reaction was cooled to room temperature
  4. customimmersed in an ice-water bath
  5. stirringthe mixture was stirred for 10 min
  6. extractionIt was extracted with EtOAc (4×75 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customto give a residue which
  10. customwas purified by flash chromatography
  11. washeluting with 20-100% EtOAc/hexanes
  12. customAppropriate fractions were collected
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3a6b9a32b05e4bf7940a6daa62156ed2
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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