Potassium Carbonate → Ethyl 3-((2-chloro-5-nitropyrimidin-4-yl)(isopropyl)amino)-2,2-difluoropropanoate

HRID 1881015ノート

反応式

HRID 1881015 の反応式
[F:1][C:2]([F:13])([CH2:8][NH:9][CH:10]([CH3:12])[CH3:11])[C:3]([O:5][CH2:6][CH3:7])=[O:4].C([O-])([O-])=O.[K+].[K+].[Cl:20][C:21]1[N:26]=[C:25](Cl)[C:24]([N+:28]([O-:30])=[O:29])=[CH:23][N:22]=1>CC(C)=O.ClCCl>[Cl:20][C:21]1[N:26]=[C:25]([N:9]([CH:10]([CH3:12])[CH3:11])[CH2:8][C:2]([F:13])([F:1])[C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:24]([N+:28]([O-:30])=[O:29])=[CH:23][N:22]=1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 5212662,4-Dichloro-5-nitropyrimidineHCID 86635897Ethyl 2,2-difluoro-3-(isopropylamino)propanoate

生成物 1

HCID 86635898Ethyl 3-((2-chloro-5-nitropyrimidin-4-yl)(isopropyl)amino)-2,2-difluoropropanoate収率 72.4%

試薬・触媒・溶媒 2

HCID 180Acetone溶媒2 回HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

Ethyl 2,2-difluoro-3-(isopropylamino)propanoate (1.50 g, 7.68 mmol) was dissolved in acetone and K2CO3 (2.12 g, 15.3 mmol) was added. The solution was purged with nitrogen gas and cooled to 0° C. A solution of 2,4-dichloro-5-nitropyrimidine (1.64 g, 8.45 mmol) in acetone (10 mL) was added dropwise at 0° C. over 1 h. The reaction mixture was allowed to slowly warm to room temperature and stirred overnight. It was diluted with dichloromethane (50 mL) and filtered thru a celite plug. The filtrate was concentrated in vacuo and the residue purified by flash column chromatography on silica gel (120 g SiO2, hexanes:ethyl acetate 10:1-3:1) to afford the title compound as a yellow oil (1.96 g, 72%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J=6.82 Hz, 6 H) 1.34 (t, J=7.20 Hz, 3 H) 3.63-3.75 (m, 1 H) 4.24 (t, J=13.14 Hz, 2 H) 4.34 (q, J=7.07 Hz, 2 H) 8.74 (s, 1 H).

後処理

  1. customThe solution was purged with nitrogen gas
  2. temperatureto slowly warm to room temperature
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue purified by flash column chromatography on silica gel (120 g SiO2, hexanes:ethyl acetate 10:1-3:1)

出典と根拠

ORDレコード
ord-4490a2b914b6442db9bba70518cce06d
出典データセット
uspto-grants-2012_11
特許番号
US08318727B2

反応ノート

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