Methanol → 4-methyl-3-oxo-N-phenylpentanamide

反応式

CCC(O[C:6]([CH:8]([CH3:10])[CH3:9])=[O:7])=O.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N([CH2:23][CH3:24])CC)C.C[OH:26]>>[CH3:10][CH:8]([CH3:9])[C:6](=[O:7])[CH2:24][C:23]([NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:26]

参加物

反応物 4

HCID 887Methanol

HCID 6115Aniline

HCID 8471Triethylamine

HCID 22025518HCID 22025518、化合物

生成物 1

HCID 102198994-methyl-3-oxo-N-phenylpentanamide収率 92.7%

反応条件

温度: 82.5 °C

実験手順

Methyl isobutyryl acetate (100 g, 0.693 mol) is placed in a 4 neck RB flask equipped with a stirring rod, thermometer socket and a distillation condenser. Aniline (71 g, 0.762 mol) and triethylamine (15 g, 0.148 mol) are added and the contents are heated to 80-85° C. under agitation. The contents are maintained at 80-85° C. for lhr and the temperature is gradually raised to 120-125° C. The reaction is maintained for 4-6 hours, during which period methanol formed in the reaction is collected (48 ml). The reaction is continued till methanol no longer distills out the contents are cooled to 25-30° C. The reaction mixture is quenched with 2N hydrochloric acid (200 ml) and extracted with methylene chloride (100 ml). The aqueous layer is extracted twice with methylene chloride (2×100 ml). The combined methylene chloride extract (300 ml) is sequentially washed with 1N hydrochloric acid (50 ml), 5% aqueous sodium bicarbonate (50 ml) and 5% aq. sodium chloride (50 ml). The organic layer is concentrated to remove methylene chloride on a water bath at 50-55° C., traces of methlyene chloride are finally removed under vacuum. 4-Methyl-3-oxo-N-phenyl pentanamide (132 g, 92.7%, HPLC purity 98.85%) thus obtained is used in next step as such.