Aluminium lithium hydride → (R)-3-((1-Methylpyrrolidin-2-yl)methyl)-5-vinyl-1H-indole

HRID 610057Notes

Reaction equation

HRID 610057 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH:7]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:18]([C@H:20]1[CH2:24][CH2:23][CH2:22][N:21]1[C:25](OCC1C=CC=CC=1)=O)=O)=[CH2:8]>C1COCC1>[CH:7]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH2:18][C@H:20]1[CH2:24][CH2:23][CH2:22][N:21]1[CH3:25])=[CH2:8]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 54294345(R)-5-vinyl-3-[(N-carbobenzyloxypyrrolidin-2-yl) carbonyl]-1H-indole

Product 1

HCID 10220397(R)-3-((1-Methylpyrrolidin-2-yl)methyl)-5-vinyl-1H-indoleYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution (R)-3-(N-Benzyloxycarbonylpyrrolidin-2-ylcarbonyl )-5-bromo-1H-indole (Example 5a, 252 mg, 0.59 mmol), tributyl(vinyl)tin (0.20 mL, 0.68 mmol) and tetrakistriphenyphosphine palladium (0) (84 mg, 0.073 mmol) in anhydrous DMF (3 mL) was stirred at 95-100° C. for 1 day. After cooling to room temperature, the product was taken into ethyl acetate, filtered through celite, washed with water (2×) and brine (1×), dried over sodium sulfate and the solvent was removed in vacuo. Flash chromatography on silica gel (60-100% ethyl acetate in hexanes) yielded (R)-5-vinyl-3-[(N-carbobenzyloxypyrrolidin-2-yl)carbonyl]-1H-indole (115 mg, 52%). A solution of LAH (0.77 mL, 1M in THF, 0.77 mmol) was added slowly to a cooled (0° C.) solution of (R)-5-vinyl-3-[(N-carbobenzyloxypyrrolidin-2-yl) carbonyl]-1H-indole (115 mg, 0.31 mmol) in THF (5 mL). Once the addition was completed, the reaction mixture was stirred at reflux for 2 h prior to quenching with sodium sulfate decahydrate. The product was taken into ethyl acetate, filtered to remove the solid residue, and the solvent was removed in vacuo. Flash chromatography on silica gel (5% 2M methanolic ammonia in dichloromethane) yielded (R)-5-vinyl-3-[(N-methylpyrrolidin-2-yl) methyl]-1H-indole (52 mg, 71%). HRMS-FAB+ for C16H20N2 : calculated MH+ :241.17047; found MH+ :241.17036.

Workup

  1. additionOnce the addition
  2. temperatureat reflux for 2 h
  3. customto quenching with sodium sulfate decahydrate
  4. filtrationfiltered
  5. customto remove the solid residue
  6. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-2e7702dd233c47179838b3856761ec9c
Source dataset
uspto-grants-1999_12
Patent number
US05998462

Reaction notes

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