Methyl malonyl chloride → Methyl 3-((2-fluorophenyl)(methyl)amino)-3-oxopropanoate

HRID 418679

反応式

HRID 418679 の反応式
Cl[C:2](=[O:8])[CH2:3][C:4]([O:6][CH3:7])=[O:5].[F:9][C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=1[NH:12][CH3:13]>C(Cl)Cl>[F:9][C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=1[N:12]([CH3:13])[C:2](=[O:8])[CH2:3][C:4]([O:6][CH3:7])=[O:5]

参加物

4

反応物 2

HCID 123460Methyl malonyl chlorideHCID 27590102-Fluoro-N-methylaniline

生成物 1

HCID 58790179Methyl 3-((2-fluorophenyl)(methyl)amino)-3-oxopropanoate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a solution of methyl 3-chloro-3-oxopropanoate (1.75 mL, 15.99 mmol) in dry DCM (32 ml) was added 2-fluoro-N-methylaniline (2 g, 15.99 mmol) and the reaction mixture was stirred at 0° C. for 1 h, evaporated then redissolved in EtOAc, washed with dilute NaHCO3, and brine. The organic phase was dried over sodium sulfate, and concentrated under reduced pressure to afford methyl 3-((2-fluorophenyl)(methyl)amino)-3-oxopropanoate as yellow oil which was used without further purification (3.3 g, 16 mmol, 97%, crude). To a solution of this material (3.3 g, 16 mmol) in THF (16 ml) and water (16 ml) was added LiOHH2O (1.35 g, 31.5 mmol) and the reaction mixture was stirred overnight, evaporated (to remove the THF) and then extracted with EtOAc. The aqueous phase was acidified to pH˜1 by addition of 1N HCl and extracted with EtOAc. The solution was dried over Na2SO4, filtered and concentrated under reduced pressure to afford the title compound 245 as a brown solid, which was used without further purification (2.75 g, 13.03 mmol, 81% yield). MS (m/z): (M+1) 218.0 (88%), (2M+Li) 429.0 (100%).

後処理

  1. customevaporated
  2. dissolutionthen redissolved in EtOAc
  3. washwashed with dilute NaHCO3, and brine
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-af84ee52720a4397ace7f65f3c8cb1d9
出典データセット
uspto-grants-2012_01
特許番号
US08093264B2

関連ノート

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