Valeryl chloride → N-((2'-Cyano(1,1'-biphenyl)-4-yl)methyl)-N-(1-oxopentyl)-L-valine methyl ester

HRID 1443315Notes

Reaction equation

HRID 1443315 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:25])[C@H:5]([CH:22]([CH3:24])[CH3:23])[NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]#[N:21])=[CH:10][CH:9]=1.C(=O)(O)[O-].[Na+].[C:31](Cl)(=[O:36])[CH2:32][CH2:33][CH2:34][CH3:35]>O.C1(C)C=CC=CC=1>[CH3:2][O:3][C:4](=[O:25])[C@H:5]([CH:22]([CH3:23])[CH3:24])[N:6]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]#[N:21])=[CH:10][CH:9]=1)[C:31](=[O:36])[CH2:32][CH2:33][CH2:34][CH3:35]

Participants

6

Reactant 3

HCID 61186Valeryl chlorideHCID 516892Sodium BicarbonateHCID 16744793N-(2'-Cyanobiphenyl-4-ylmethyl)-L-valine Methyl Ester Hydrochloride

Product 1

HCID 16744795N-((2'-Cyano(1,1'-biphenyl)-4-yl)methyl)-N-(1-oxopentyl)-L-valine methyl esterYield 107.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
28 °C

Procedure

150 g N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester hydrochloride was charged into a round bottomed flask containing a mixture of sodium bicarbonate (158.1 g), water (450 ml) and toluene (900 ml). The contents were stirred at 28° C. for 25 minutes and then cooled to 0° C. 110.9 g of valeryl chloride was added slowly to the reaction mass at 0-20° C. over about 55 minutes. The reaction mass was stirred at about 2-4° C. for about 2 hours. Reaction completion was confirmed by thin layer chromatography and the reaction mixture was allowed to attain 28° C. 450 ml of water was added to the reaction mass and stirred for about 20 minutes. The organic layer was separated, washed with a solution of sodium bicarbonate (30 g) in water (450 ml) twice, followed by washing with water (450 ml). The organic layer was concentrated under reduced pressure at 60-68° C. to obtain 183 g of the title compound.

Workup

  1. additioncontaining
  2. temperaturecooled to 0° C
  3. stirringThe reaction mass was stirred at about 2-4° C. for about 2 hours
  4. customReaction completion
  5. customto attain 28° C
  6. stirringstirred for about 20 minutes
  7. customThe organic layer was separated
  8. washwashed with a solution of sodium bicarbonate (30 g) in water (450 ml) twice
  9. washby washing with water (450 ml)
  10. concentrationThe organic layer was concentrated under reduced pressure at 60-68° C.

Sources & evidence

ORD record
ord-9abacb88bd514a0fb0a6d8a5e8aba653
Source dataset
uspto-grants-2010_02
Patent number
US07659406B2

Reaction notes

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