Cesium carbonate → 1,1-Dimethylethyl 4-(6-fluoro-2-methyl-5-quinolinyl)-1-piperazinecarboxylate

HRID 2373599

反応式

HRID 2373599 の反応式
Br[C:2]1[C:11]([F:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH3:13])=[N:7]2.[N:14]1([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.C1(P(C2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=C(C3C4C(=CC=CC=4)C=CC=3)C3C(C=2)=CC=CC=3)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1>[F:12][C:11]1[C:2]([N:17]2[CH2:16][CH2:15][N:14]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:19][CH2:18]2)=[C:3]2[C:8](=[CH:9][CH:10]=1)[N:7]=[C:6]([CH3:13])[CH:5]=[CH:4]2

参加物

6

反応物 4

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 130353135-Bromo-6-fluoro-2-methylquinolineHCID 18630801Bis(diphenylphosphino)-1,1'-binaphthyl

生成物 1

HCID 574443131,1-Dimethylethyl 4-(6-fluoro-2-methyl-5-quinolinyl)-1-piperazinecarboxylate収率 65.8%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
120 °C

実験手順

A mixture of 5-bromo-6-fluoro-2-methylquinoline (Chem. Pharm. Bull., 1989, 37(8), 2103-8, 0.285 g), 1,1-dimethylethyl 1-piperazinecarboxylate (0.265 g, 1.2 equiv.), Pd(OA)2 (15 mol %, 0.04 g), bis(diphenylphosphino)-1,1′-binaphthyl (BINAP, 30 mol %, 0.221 g), cesium carbonate (1.5 equiv. 0.580 g) and toluene (3.5 mL) were stirred at 120° C. for 20 h in a sealed tube. The mixture was cooled to room temperature and partitioned between ethyl acetate and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. This crude product was purified by flash chromatography [SiO2; DCM-MeOH (99:1)→(90:10)] to afford the title compound as colourless solid (0.270 g, 65% yield).

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate and brine
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThis crude product was purified by flash chromatography [SiO2; DCM-MeOH (99:1)→(90:10)]

出典と根拠

ORDレコード
ord-0a307ebf7886454897f8d98a77bcccbc
出典データセット
uspto-grants-2008_12
特許番号
US07459456B2

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