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

HRID 5684
Notes
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Reaction equation

HRID 5684 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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 (XVIII). 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 (XVIII) 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-dimethylaniline, 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. Preferably the reaction is carried out in the presence of 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide and the triethylamine in ethanol at about 75°-80° C. for about 24 hours. The compound of Formula XVII is reacted with a compound of Formula ##STR45## wherein R10 and R11 are alkyl of one to either carbon atoms or R10 and R11 together are ##STR46## --CH2CH2 --or --CH2CH2CH2 --in the presence of a catalyst of Formula

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-030dd67a47da476ca971ca42ed1f5543
Source dataset
uspto-grants-1993_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05245047

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes