Aluminum(III) Chloride → HCID 23288871, compound

HRID 368849Notes

Reaction equation

HRID 368849 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-:7].[Al+3].[Cl-].[Cl-].[CH:11]1([CH2:20][C:21]([N:23]2[CH2:28][CH2:27][N:26]([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)[CH2:25][CH2:24]2)=O)[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13][CH2:12]1>C1COCC1>[ClH:7].[ClH:7].[CH:11]1([CH2:20][CH2:21][N:23]2[CH2:28][CH2:27][N:26]([C:29]3[CH:30]=[CH:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=3)[CH2:25][CH2:24]2)[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 6451240Aluminum(III) ChlorideHCID 15859038HCID 15859038, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 23288871HCID 23288871, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of lithium aluminum hydride (1.9 g, 50 mmol) in THF (250 ml) is cooled to -20° under a nitrogen atmosphere. Aluminum chloride (6.7 g, 50 mmol) is added slowly via a powder funnel and the mixture is stirred for 10 min. A mixture of 4-[(indan-1-yl)acetyl]-1-(4-methoxyphenyl)piperazine (CXI, EXAMPLE 68, 8.76 g, 25 mmol) in THF (100 ml) is added dropwise over 10 min. The mixture is allowed to warm to 0-5° and stirred for 1 hr. The reaction is quenched with sodium hydroxide (20%) and extracted with methylene chloride (2×800 ml). The organic phase is washed with water, saline, dried (magnesium sulfate), filtered and concentrated under reduced pressure. The concentrate is purified by liquid chromatography on silica gel 60 (230-400 mesh, 400 g), eluting with hexane/ethyl acetate (1/2). The appropriate fractions homogeneous by TLC are combined and concentrated under reduced pressure to give the free base of the title compound, which is converted into the hydrochloric acid salt and crystallized from ethyl acetate/methanol to give the title compound, mp 237-239°; NMR (CDCl3, TMS) 7.80-6.92, 3.84 and 4.82-1.50 δ.

Workup

  1. temperatureis cooled to -20° under a nitrogen atmosphere
  2. additionis added dropwise over 10 min
  3. temperatureto warm to 0-5°
  4. stirringstirred for 1 hr
  5. customThe reaction is quenched with sodium hydroxide (20%)
  6. extractionextracted with methylene chloride (2×800 ml)
  7. washThe organic phase is washed with water, saline
  8. dry with materialdried (magnesium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe concentrate is purified by liquid chromatography on silica gel 60 (230-400 mesh, 400 g)
  12. washeluting with hexane/ethyl acetate (1/2)
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-597b80121dec4a8a9458dabc54626f59
Source dataset
uspto-grants-2000_10
Patent number
US06133446

Reaction notes

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