Aluminium lithium hydride → HCID 66588630, compound

HRID 1092730Notes

Reaction equation

HRID 1092730 reaction equation
Br[C:2]1[CH:3]=[C:4]2[O:23][CH2:22][O:21][C:5]2=[C:6]2[C:15]=1[CH2:14][CH:13]1[CH:8]([CH2:9][CH2:10][CH2:11][N:12]1[C:16](=O)[CH2:17][CH3:18])[C:7]2=O.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH2:16]([N:12]1[CH2:11][CH2:10][CH2:9][C@H:8]2[C@@H:13]1[CH2:14][C:15]1[C:6]([CH2:7]2)=[C:5]2[O:21][CH2:22][O:23][C:4]2=[CH:3][CH:2]=1)[CH2:17][CH3:18]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 57608059HCID 57608059, compound

Product 1

HCID 66588630HCID 66588630, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Compound 25 (0.34 g dissolved in THF (5 mL)) was added to a suspension of LAH (0.3 g) in THF (5 mL) at 0° C. The mixture was stirred at for 40 min, before it was quenched with ice/water and basified with 27% aqueous NaOH. The product was extracted into 2-methyl-THF. The organic layer was washed with sat. aqueous NaHCO3, dried (MgSO4), and concentrated in vacuo. The residue was dissolved in MeOH (3 mL) and treated with a few mg of 5% Pd/C, 37% aqueous HCl (10 drops), and hydrogen gas (3 bar) at 50° C. for ˜1 h and further at rt (1 bar hydrogen pressure) overnight. Next morning, a few mg of additional 5% Pd/C were added, and the mixture was hydrogenated (3 bar) at 50° C. overnight (this procedure was repeated several times over a total of four days). The catalyst was filtered off, and the filtrate was concentrated in vacuo. The residue was partitioned between 2M aqueous NaOH and DCM. The organic layer was washed with sat. aqueous NaHCO3, dried (MgSO4), and diluted with 2M HCl in Et2O and concentrated in vacuo. The residue was dissolved in MeOH, and treated with 2M HCl in Et2O at 0° C. The precipitated product was isolated by filtration. Yield of example 5d1: 53 mg as a white solid. LC/MS (method 111): RT 0.71 min, ELSD 100%, UV 61%. MH+: 274.1.

Workup

  1. customwas quenched with ice/water
  2. extractionThe product was extracted into 2-methyl-THF
  3. washThe organic layer was washed with sat. aqueous NaHCO3
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in MeOH (3 mL)
  7. additiontreated with a few mg of 5% Pd/C, 37% aqueous HCl (10 drops), and hydrogen gas (3 bar) at 50° C. for ˜1 h and further at rt (1 bar hydrogen pressure) overnight
  8. additionNext morning, a few mg of additional 5% Pd/C were added
  9. customat 50° C.
  10. customovernight
  11. customover a total of four days
  12. filtrationThe catalyst was filtered off
  13. concentrationthe filtrate was concentrated in vacuo
  14. customThe residue was partitioned between 2M aqueous NaOH and DCM
  15. washThe organic layer was washed with sat. aqueous NaHCO3
  16. dry with materialdried (MgSO4)
  17. additiondiluted with 2M HCl in Et2O
  18. concentrationconcentrated in vacuo
  19. dissolutionThe residue was dissolved in MeOH
  20. additiontreated with 2M HCl in Et2O at 0° C
  21. customThe precipitated product was isolated by filtration
  22. customRT 0.71 min, ELSD 100%, UV 61%

Sources & evidence

ORD record
ord-953fb516affb417196c13aa4c8d31ba1
Source dataset
uspto-grants-2012_03
Patent number
US08129530B2

Reaction notes

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