Toluene → 4-(2-Methoxy-quinolin-5-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1373642ノート

反応式

HRID 1373642 の反応式
C1(C)C=CC=CC=1.Br[C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH:11]=[CH:12][C:13]([O:19][CH3:20])=[N:14]2.[C:21]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].CC([O-])(C)C.[Na+]>C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>[C:24]([O:23][C:21]([N:28]1[CH2:33][CH2:32][N:31]([C:9]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:10]=2[CH:11]=[CH:12][C:13]([O:19][CH3:20])=[N:14]3)[CH2:30][CH2:29]1)=[O:22])([CH3:27])([CH3:25])[CH3:26]

参加物

8

反応物 4

HCID 1140TolueneHCID 143452tert-Butyl piperazine-1-carboxylateHCID 142209695-Bromo-2-methoxyquinolineHCID 23676156Sodium t-butoxide

生成物 1

HCID 694222494-(2-Methoxy-quinolin-5-yl)-piperazine-1-carboxylic acid tert-butyl ester収率 66%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 27342162-(Dicyclohexylphosphino)biphenyl触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

A third intermediate compound, 2-Methoxy-5-piperazin-1-yl-quinoline, was produced as follows: To an oven-dried flask, under nitrogen, was added Pd(OAc)2 (0.03 g, 0.13 mmol) and 2-(dicyclohexylphosphino)biphenyl (0.045 g, 0.13 mmol). The flask was evacuated and refilled with nitrogen. The following materials were added in the following order: degassed toluene (10 mL), 5-bromo-2-methoxy-quinoline (0.76 g, 3.23 mmol), 1-Boc-piperazine (0.72 g, 3.87 mmol), and NaOtBu (0.43 g, 4.52 mmol). The mixture was stirred at 80° C. for 1.5 h. After cooling to room temperature, the mixture was diluted with ethyl acetate and filtered through celite. The filtrate was concentrated in vaccuo and purified by chromatography on silica gel (10% EtOAc/Hexane) to give 4-(2-methoxy-quinolin-5-yl)-piperazine-1-carboxylic acid tert-butyl ester as a yellowish solid (0.73 g, 66%). 1H NMR (400 MHz, CDCl3) δ: 8.35 (d, 1H), 7.60 (m, 2H), 7.00 (d, 1H), 6.90 (d, 1H), 4.05 (s, 3H), 3.75 (m, 4H), 3.00 (m, 4H), 1.50 (s, 9H).

後処理

  1. customThe flask was evacuated
  2. additionrefilled with nitrogen
  3. additionThe following materials were added in the following order
  4. temperatureAfter cooling to room temperature
  5. filtrationfiltered through celite
  6. concentrationThe filtrate was concentrated in vaccuo
  7. custompurified by chromatography on silica gel (10% EtOAc/Hexane)

出典と根拠

ORDレコード
ord-464fc088001c4c3fb4669856f3448c1f
出典データセット
uspto-grants-2007_01
特許番号
US07160888B2

反応ノート

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