盐酸 → 1-(2-甲氧基苯基)哌嗪盐酸盐

HRID 1750141笔记

反应方程式

HRID 1750141 反应方程式
[ClH:1].[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11]1>CCOC(C)=O>[ClH:1].[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1

参与物

4

反应物 2

HCID 313盐酸HCID 13560548Tert-butyl 4-(2-methoxyphenyl)piperazine-1-carboxylate

产物 1

HCID 98994021-(2-甲氧基苯基)哌嗪盐酸盐收率 42%

试剂、催化剂与溶剂 1

HCID 8857乙酸乙酯溶剂2 次

实验过程

A well-dried flask was first charged with 1-bromo-2-methoxybenzene (4.0 g, 21.3 mmol) and piperazine (2.2 g, 25.6 mmol), which was evacuated and backfilled with N2 through a balloon under gentle warming (40° C.). Toluene was charged and the mixture was bubbled with N2 for 10 min, then BINAP (398 mg, 0.64 mmol) and Pd2 dba3 (195 mg, 0.21 mmol) was added to the mixture. After the addition of DBU (3.8 mL), the solution was warmed at 60-70° C. while a fine powder of tBuONa (3.5 g, 31.9 mmol) was added in one portion to start the amination. After the reaction mixture cooled to rt, (Boc)2O (11.6 g, 53.2 mmol) was dissolved in DCM and added dropwise to the reaction mixture, then stirred at rt for 3 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layers were washed with brine, dried over anhydrous Na2SO4, concentrated in vacuo and purified by flash chromatography on silica gel column (elution with PE/EtOAc=10:1) to give tert-butyl 4-(2-methoxyphenyl)piperazine-1-carboxylate as a white solid. Excess HCl in EtOAc was added dropwise to a solution of tert-butyl 4-(2-methoxyphenyl)piperazine-1-carboxylate in EtOAc and the reaction mixture was stirred at rt for 1.5 h. Filtration gave 1-(2-methoxyphenyl)piperazine hydrochloride salt (intermediate 55) (2.6 g, 42%) as a white solid. HPLC: 99%, RT 1.586 min. MS (ESI) m/z 193.1 [M+H]+.

后处理

  1. filtrationFiltration

来源与证据

ORD记录
ord-69be39dbe4424e38ab3185cf28156001
来源数据集
uspto-grants-2015_10
专利号
US09156822B2

反应笔记

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