Piperazine → HCID 18436771、化合物

HRID 456433ノート

反応式

HRID 456433 の反応式
[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]

参加物

8

反応物 4

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

生成物 1

HCID 18436771HCID 18436771、化合物収率 93%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
95 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-b945508cc3f346f29dc68afcd79b546d
出典データセット
uspto-grants-2007_03
特許番号
US07186715B2

反応ノート

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