Valproic Acid → HCID 22859404, compound

HRID 1440402Notes

Reaction equation

HRID 1440402 reaction equation
C([O:8][C:9]([NH:11][C@H:12]([C:17]([NH:19][C@H:20]([CH2:31][OH:32])[CH2:21][C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[NH:24][CH:23]=1)=[O:18])[C@H:13]([CH2:15][CH3:16])[CH3:14])=O)C1C=CC=CC=1.C(O)(=O)[CH:34]([CH2:38][CH2:39][CH3:40])[CH2:35][CH2:36][CH3:37].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.ClCCl.[C].[Pd].CO.C1COCC1>[C:9]([NH:11][C@H:12]([C:17]([NH:19][C@H:20]([CH2:31][OH:32])[CH2:21][C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[NH:24][CH:23]=1)=[O:18])[C@H:13]([CH2:15][CH3:16])[CH3:14])(=[O:8])[CH:34]([CH2:38][CH2:39][CH3:40])[CH2:35][CH2:36][CH3:37]

Participants

9

Reactant 4

HCID 3121Valproic AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10836729HCID 10836729, compound

Product 1

HCID 22859404HCID 22859404, compoundYield 84.8%

Reagents, catalysts & solvents 4

HCID 178418390HCID 178418390, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of N-benzyloxycarbonyl-(L)-isoleucyl-(L)-tryptophanol(2.14 g), palladium-carbon (5%, 50% wet, 1.0 g) and methanol-THF (5:1, 30 ml) was subjected to catalytic hydrogenation at room temperature and atomospheric pressure. After the catalyst was filtered off, the filterate was concentrated under reduced pressure to yield an oily substance. The oil and valproic acid (0.71 g) were dissolved in N,N-dimethylformamide (20 ml), and 1-hydroxybenzotriazole (HOBt) (0.82 g) and a solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSCD·HCl)(1.13 g) in dichloromethane (20 ml) were added thereto at 0° C. After stirring at 0° C. for 1 hour and at room temperature for 15 hours, the reaction mixture was concentrated under reduced pressure and the residue was suspended in ethyl acetate (120 ml). The mixture was successively washed with 10% aqueous citric acid solution, water, saturated aqueous sodium hydrogen carbonate and brine, and dried (MgSO4). The organic solvent was evaporated off to yield N-valproyl-(L)-isoleucyl-(L)-tryptophanol (1.78 g, 84.8%) as crystals. Recrystallization from ethyl acetate-hexane gave colorless needles.

Workup

  1. customwas subjected to catalytic hydrogenation at room temperature
  2. filtrationAfter the catalyst was filtered off
  3. concentrationthe filterate was concentrated under reduced pressure
  4. customto yield an oily substance
  5. customat 0° C
  6. concentrationthe reaction mixture was concentrated under reduced pressure
  7. washThe mixture was successively washed with 10% aqueous citric acid solution, water, saturated aqueous sodium hydrogen carbonate and brine
  8. dry with materialdried (MgSO4)
  9. customThe organic solvent was evaporated off

Sources & evidence

ORD record
ord-5dbd89ebc01647fdab7fc1dd08270956
Source dataset
uspto-grants-1996_03
Patent number
US05498728

Reaction notes

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