Beta-Alanine → 2-Benzylidene-4-methyl-3-oxo-N-phenylpentanamide

HRID 1886264Notes

Reaction equation

HRID 1886264 reaction equation
[CH3:1][CH:2]([CH3:15])[C:3](=[O:14])[CH2:4][C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:6].CC(C)C(=O)CC(OC)=O.NC1C=CC=CC=1.C(N)CN.[CH:37](=O)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.N1CCCCC1.NCCC(O)=O>C1(C)C=CC=CC=1.O.CCCCCC.CCCCCCC.C(O)(=O)C>[CH3:1][CH:2]([CH3:15])[C:3](=[O:14])[C:4](=[CH:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:6]

Participants

13

Reactant 7

HCID 239Beta-AlanineHCID 240BenzaldehydeHCID 3301Ethylenediamine2×HCID 6115AnilineHCID 8082PiperidineHCID 2759969Methyl 4-methyl-3-oxopentanoateHCID 102198994-methyl-3-oxo-N-phenylpentanamide2×

Product 1

HCID 533948662-Benzylidene-4-methyl-3-oxo-N-phenylpentanamide

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolvent3×HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 8058HexaneSolventHCID 8900HeptaneSolvent

Procedure

4-Methyl-3-oxo-N-phenylpentanamide (XIX) is obtained by heating a mixture of methyl 4-methyl-3-oxopentanoate (XX), aniline and ethylene diamine in toluene. 4-Methyl-3-oxo-N-phenylpentanamide (XIX) is subsequently reacted with benzaldehyde in the presence of a catalyst such as, for example, piperidine and glacial acetic acid, ethylene diamine and glacial acetic acid, β-alanine and glacial acetic acid, and the like in an inert solvent such as, for example, toluene, heptane, hexane, and the like for about 24 to about 36 hours at about 60° to about 120° C. with the removal of water to afford 4-methyl-3-oxo-N-phenyl-2-(phenylmethylene)pentanamide (XVIIl). Preferably the reaction is carried out with β-alanine and glacial acetic acid at reflux for about 24 hours in hexane. The 4-methyl-3-oxo-N-phenyl-2-(phenylmethylene)pentanamide (XVI) is reacted with 4-fluorobenzaldehyde in the presence of a catalyst such as, for example, 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride, 3,4-dimethyl-5-(2-hydroxyethyl)thiazolium iodide, 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide, thiamine hydrochloride, and the like, and a base such as, for example, N,N-diisopropylethylamine, pyridine, N,N-dimethylaniine, triethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), 4-dimethylaminopyridine (DMAP), N,N,N',N'-tetramethylethylenediamine (TMEDA) and the like, either neat or in the presence of a solvent such as, for example, tetrahydrofuran, tertiary-butyl methyl ether, ethanol, dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone, acetonitrile, methylisobutyl ketone, ethyl acetate, isopropanol, pyridine and the like for about 20 to about 30 hours under anhydrous conditions at about room temperature to about the reflux temperature of the solvent to afford the compound of Formula XVII.

Workup

  1. temperatureby heating
  2. customlike for about 24 to about 36 hours
  3. customat about 60° to about 120° C.

Sources & evidence

ORD record
ord-83111156d89d492682844aad4ae169e9
Source dataset
uspto-grants-1992_09
Patent number
US05149837

Reaction notes

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