L-Valine → HCID 11223028, compound

HRID 2116619Notes

Reaction equation

HRID 2116619 reaction equation
[OH-].[Na+].[NH2:3][C@H:4]([C:8]([OH:10])=[O:9])[CH:5]([CH3:7])[CH3:6].[CH:11]([C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:15][CH:14]=1)=O.C(N(CC)CC)C.[C:34](Cl)(=[O:39])[CH2:35][CH2:36][CH2:37][CH3:38]>CO.ClCCl.C(OCC)(=O)C.C(O)(C)C>[CH:5]([CH:4]1[C:8](=[O:10])[O:9][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=3)=[CH:15][CH:14]=2)[N:3]1[C:34](=[O:39])[CH2:35][CH2:36][CH2:37][CH3:38])([CH3:7])[CH3:6]

Participants

10

Reactant 5

HCID 6287L-ValineHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 61186Valeryl chlorideHCID 13940624'-Formyl-[1,1'-biphenyl]-2-carbonitrile

Product 1

HCID 11223028HCID 11223028, compoundYield 50%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

2.0 g of NaOH powder (49.5 mmoles) and L-valine 6.5 g (55.5 mmoles) are reacted in 50 ml of dry methanol. The mixture is stirred at 25° C. for 10 minutes, then evaporated in rotary evaporator, added with 8.7 g (42.2 mmoles) of 4′-formyl biphenyl-2-carbonitrile and 50 ml of isopropanol and left under stirring for 1 hour. The solution is concentrated at 60° C. under reduced pressure to obtain a solid or oily residue, which is kept at 50° C. under reduced pressure for 3 hours to remove the water formed during the reaction. A solid is obtained in molar yield equivalent to 90% (12 g, 38.0 mmoles). The solid is suspended in 80 ml of dry dichloromethane and heated to reflux under mild nitrogen stream. 2.1 g of triethylamine (20.8 mmoles) and 7.9 g of valeryl chloride (65.7 mmoles) are added to the mixture, that is refluxed for 2 hours, then cooled to 25° C. The organic phase is washed three times with 50 ml of water and concentrated under reduced pressure at 25-30° C., to obtain an oily residue. 50 ml of ethyl acetate are added and the organic phase is washed with a weakly basic NaOH solution, then with water to neutrality. The organic phase is washed with a sodium bisulfite solution, then with water, dried over sodium sulfate, filtered and evaporated under reduced pressure. The oily residue is taken up with isopropanol from which the title product crystallizes (8.2 g, 21.1 mmoles; molar yield: 50%).

Workup

  1. customevaporated in rotary evaporator
  2. waitleft
  3. stirringunder stirring for 1 hour
  4. concentrationThe solution is concentrated at 60° C. under reduced pressure
  5. customto obtain a solid or oily residue, which
  6. waitis kept at 50° C. under reduced pressure for 3 hours
  7. customto remove the water
  8. customformed during the reaction
  9. customA solid is obtained in molar yield equivalent to 90% (12 g, 38.0 mmoles)
  10. temperatureheated
  11. temperatureto reflux under mild nitrogen stream
  12. temperatureis refluxed for 2 hours
  13. temperaturecooled to 25° C
  14. washThe organic phase is washed three times with 50 ml of water
  15. concentrationconcentrated under reduced pressure at 25-30° C.
  16. customto obtain an oily residue
  17. washthe organic phase is washed with a weakly basic NaOH solution
  18. washThe organic phase is washed with a sodium bisulfite solution
  19. dry with materialwith water, dried over sodium sulfate
  20. filtrationfiltered
  21. customevaporated under reduced pressure
  22. customcrystallizes (8.2 g, 21.1 mmoles; molar yield: 50%)

Sources & evidence

ORD record
ord-dd8e17ae72134955b6abf02dc82e1b92
Source dataset
uspto-grants-2008_10
Patent number
US07439261B2

Reaction notes

Loading…