Aluminium lithium hydride → HCID 22638687, compound

HRID 1836626Notes

Reaction equation

HRID 1836626 reaction equation
[CH3:1][N:2]([CH3:20])[C:3]([C@@H:5]1[CH2:7][C@H:6]1[C:8]([C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:19])[CH:17]=2)[NH:12][CH:11]=1)=O)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[F:19][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]=[C:10]2[CH2:8][CH:6]1[CH2:7][CH:5]1[CH2:3][N:2]([CH3:1])[CH3:20]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 69839823HCID 69839823, compound

Product 1

HCID 22638687HCID 22638687, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Trans-2-(5-fluoro-3-indolylcarbonyl)cyclopropanecarboxylic acid dimethylamide (0.27 g, 1 mmol) in tetrahydrofuran was added to a suspension of lithium aluminum hydride (0.2 g, 0.5 mmol) in tetrahydrofuran. The mixture was heated at reflux for 4 hr and stirred at 20° for 12 hr. The reaction was quenched by the sequential addition of 0.5 ml of water, 0.5 ml 15% NaOH solution and 0.5 ml water. After stirring for 1 hr, the insoluble solids were removed by filtration and washed with acetone. The organic solution was concentrated in vacuo and the residue dissolved in methanol and purified by absorption on SCX resin washing with methanol and elution with 1 M methanolic ammonia solution. The basic elutants were concentrated in vacuo, dissolved in fresh methanol and made acidic with 12 N HCl. The acidic solution was thoroughly concentrated in vacuo to give racemic [2-(5-fluoro-1H-indol-3-ylmethyl)-cyclopropyl-methyl]-dimethylamine (165 mg). LC/MS mw=247; retention time 0.96 min. Mol wt calc1d for C15H19FN2: 246.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 4 hr
  3. customThe reaction was quenched by the sequential addition of 0.5 ml of water, 0.5 ml 15% NaOH solution and 0.5 ml water
  4. stirringAfter stirring for 1 hr
  5. customthe insoluble solids were removed by filtration
  6. washwashed with acetone
  7. concentrationThe organic solution was concentrated in vacuo
  8. dissolutionthe residue dissolved in methanol
  9. custompurified by absorption on SCX resin
  10. washwashing with methanol and elution with 1 M methanolic ammonia solution
  11. concentrationThe basic elutants were concentrated in vacuo
  12. dissolutiondissolved in fresh methanol
  13. concentrationThe acidic solution was thoroughly concentrated in vacuo

Sources & evidence

ORD record
ord-9b0bdca07b0c4454b4309489bb92a288
Source dataset
uspto-grants-2004_08
Patent number
US06777437B2

Reaction notes

Loading…