Aluminium lithium hydride → HCID 22638687, compound

HRID 1836627Notes

Reaction equation

HRID 1836627 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-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1.CCOCC>[NH3:2].[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

6

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 69839823HCID 69839823, compound

Product 2

HCID 222AmmoniaHCID 22638687HCID 22638687, compoundYield 184.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (−)-trans-2-(5-fluoro-3-indolylcarbonyl)-cyclopropanecarboxylic acid dimethylamide (180 mg, 0.66 mmol) in THF was added dropwise to a suspension of LAH (100 mg, 2.63 mmol) in THF at room temperature with stirring. The reaction was heated to reflux and stirred for 1 h. The reaction was then cooled to room temperature, diluted with ether, and quenched with aqueous NaOH (1 mL of 1 N solution). The resulting precipitate was filtered and washed with ether. The organic filtrate was concentrated in vacuo. The residue was dissolved in methylene chloride, and transferred directly to an SCX resin cartridge. The cartridge was washed with methanol, and then with methanolic ammonia (2.0 M) to give (+)-[2-(5-fluoro-1H-indol-3-ylmethyl)-cyclopropyl-methyl]-dimethylamine [150 mg, 94% yield, optical rotation +19.26° (c=1.38 mg/mL, ethanol, 20° C.)]. 1H NMR (MeOH-d4): δ7.25 (dd, J=8.8, 4.5 Hz, 1H), 7.17 (dd, J=9.9, 2.5 Hz, 1H), 6.82 (dt, J=2.4 Hz, 1H), 2.69 (dd, J=6.5 Hz, 2H), 2.29 (dd, J=4.86 Hz, 1H), 2.20 (s, 6H), 2.15 (dd, J=12.8 Hz, 1H), 0.90 (m, 1H), 0.70 (m, 1H), 0.51 (m, 1H), and 0.39 (m, 1H), FIMS: 247.3 (M+H)+.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux
  3. stirringstirred for 1 h
  4. customquenched with aqueous NaOH (1 mL of 1 N solution)
  5. filtrationThe resulting precipitate was filtered
  6. washwashed with ether
  7. concentrationThe organic filtrate was concentrated in vacuo
  8. dissolutionThe residue was dissolved in methylene chloride
  9. washThe cartridge was washed with methanol

Sources & evidence

ORD record
ord-320aea95919e4712b84d3eafb568b41e
Source dataset
uspto-grants-2004_08
Patent number
US06777437B2

Reaction notes

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