Piperazine → HCID 18436771, 화합물

HRID 456433노트

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HRID 456433 반응식
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2Br)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

참가 물질

8

반응물 4

HCID 4837PiperazineHCID 634876Binap, (A+-)-HCID 16731688HCID 16731688, 화합물HCID 23676156Sodium t-butoxide

생성물 1

HCID 18436771HCID 18436771, 화합물수율 93%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

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온도
95 °C

실험 절차

To a solution of N-boc-4-(2-bromo-phenoxy)-piperidine (13.4 g, 39.6 mmol, 1.0 eq.), piperazine (9.73 g, 113 mmol, 3.0 eq.), Pd2dba3 (1.72 g, 1.88 mmol, 0.05 eq.), BINAP (3.5 g, 5.65 mmol, 0.15 eq.) in toluene (150 mL) was added NaOtBu (5.1 g, 52.6 mmol, 1.4 eq.). The mixture was heated to 95° C. and stirred at that temperature overnight. The slurry was diluted with EtOAc and filtered through a pad of celite. The filtrate was concentrated and purified by ion exchange (SCX, 10 g) column. Further purification by flash chromatography (250 g SiO2, 40 ml/min, linear gradient 0–10% 2.0 M NH3 in MeOH/CH2Cl2 for 20 minutes and 10% 2.0 M NH3 in MeOH/CH2Cl2 for 73 minutes) afforded the final compound (12.65 g, 93%). LRMS (electrospray): 362.7 (M+1).

후처리

  1. filtrationfiltered through a pad of celite
  2. concentrationThe filtrate was concentrated
  3. custompurified by ion exchange (SCX, 10 g) column
  4. customFurther purification by flash chromatography (250 g SiO2, 40 ml/min, linear gradient 0–10% 2.0 M NH3 in MeOH/CH2Cl2 for 20 minutes and 10% 2.0 M NH3 in MeOH/CH2Cl2 for 73 minutes)

출처 및 근거

ORD 기록
ord-b945508cc3f346f29dc68afcd79b546d
출처 데이터셋
uspto-grants-2007_03
특허 번호
US07186715B2

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