Cesium carbonate → 5-(pyrrolidin-1-yl)-1H-indole

HRID 641879

Reaction equation

HRID 641879 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7](C(OC(C)(C)C)=O)[CH:6]=[CH:5]2.C([O-])([O-])=O.[Cs+].[Cs+].[NH:24]1[CH2:31][CH2:30][CH2:29][C@H:25]1C(O)=O.N1CCCC1>[Cu]I.CS(C)=O>[N:24]1([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[CH:5]3)[CH2:31][CH2:30][CH2:29][CH2:25]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 31268PyrrolidineHCID 145742L-ProlineHCID 2728482N-Boc-5-bromoindole

Product 1

HCID 592594025-(pyrrolidin-1-yl)-1H-indoleYield 383.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
95 °C

Procedure

t-Butyl 5-bromo-1H-indole-1-carboxylate (200 mg, 0.68 mmol) was placed in a 10 mL sealed tube. Cs2CO3 (440 g, 1.35 mol) was then added, followed by CuI (13 mg, 0.07 mmol), L-proline (16 mg, 0.14 mmol), DMSO (3 mL), and pyrrolidine (480 g, 6.75 mol). After sparging with nitrogen, the resulting solution was stirred at 95° C. for 18 hours. The mixture was extracted with ethyl acetate (3×40 mL), and the organic layers were combined and washed with brine. The residue was purified by column chromatography using 1:5 and 1:2 ethyl acetate/petroleum ether solvent systems. The collected fractions were combined and concentrated to give 100 mg (80%) of 5-(pyrrolidin-1-yl)-1H-indole as brown oil.

Workup

  1. customsealed tube
  2. customAfter sparging with nitrogen
  3. extractionThe mixture was extracted with ethyl acetate (3×40 mL)
  4. washwashed with brine
  5. customThe residue was purified by column chromatography
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-5234e558e6374657ab1ddbe04d978a05
Source dataset
uspto-grants-2010_04
Patent number
US07696229B2

Linked notes

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