3-(2-Chloro-phenoxy)-4-(3,3-difluoro-1-methoxycarbonyl-propylamino)-but-2-enoic acid ethyl ester → 2-[4-(2-Chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4,4-difluoro-butyric acid methyl ester

HRID 19324노트

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HRID 19324 반응식
C([O:3][C:4](=O)[CH:5]=[C:6]([O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[Cl:25])[CH2:7][NH:8][CH:9]([C:14]([O:16][CH3:17])=[O:15])[CH2:10][CH:11]([F:13])[F:12])C>C(#N)C>[CH3:17][O:16][C:14](=[O:15])[CH:9]([N:8]1[CH2:7][C:6]([O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])=[CH:5][C:4]1=[O:3])[CH2:10][CH:11]([F:13])[F:12]

참가 물질

3

반응물 1

HCID 675040683-(2-Chloro-phenoxy)-4-(3,3-difluoro-1-methoxycarbonyl-propylamino)-but-2-enoic acid ethyl ester

생성물 1

HCID 668949342-[4-(2-Chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4,4-difluoro-butyric acid methyl ester수율 75.5%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
180 °C

실험 절차

A solution of 3-(2-chloro-phenoxy)-4-(3,3-difluoro-1-methoxycarbonyl-propylamino)-but-2-enoic acid ethyl ester (1.19 g, 3.04 mmol) in acetonitrile (4 mL) was placed in a sealed microwave reaction tube and heated in a microwave reactor at 180° C. for 3 h. The mixture was then cooled to room temperature and concentrated in vacuo with silica gel (3 g). Purification by Biotage flash chromatography (Aspire 40 g column, 16% ethyl acetate/hexanes to 50% ethyl acetate/hexanes) afforded 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4,4-difluoro-butyric acid methyl ester (794 mg, 40% over two steps) as an amber oil: HR-ES-MS m/z calculated for C15H14NO4ClF2 [M+H]+ 346.0652, observed 346.0651.

후처리

  1. temperatureThe mixture was then cooled to room temperature
  2. concentrationconcentrated in vacuo with silica gel (3 g)
  3. customPurification by Biotage flash chromatography (Aspire 40 g column, 16% ethyl acetate/hexanes to 50% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-90a5dcacdd6f4055a3c6ec6c70342227
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741327B2

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