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

HRID 418679

반응식

HRID 418679 반응식
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]

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-af84ee52720a4397ace7f65f3c8cb1d9
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093264B2

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