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

HRID 1373642노트

반응식

HRID 1373642 반응식
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]

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 27342162-(Dicyclohexylphosphino)biphenyl촉매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-464fc088001c4c3fb4669856f3448c1f
출처 데이터셋
uspto-grants-2007_01
특허 번호
US07160888B2

반응 노트

불러오는 중…