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R-(+)-1,1'-联萘-2,2'-双二苯膦 → 1-[3-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-4-(2-methylpyridin-4-yl)piperazine

HRID 1021237
笔记
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反应方程式

HRID 1021237 反应方程式
Br[C:2]1[C:3]([F:17])=[C:4]([CH:14]=[CH:15][CH:16]=1)[CH2:5][O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].[CH3:18][C:19]1[CH:24]=[C:23]([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH:22]=[CH:21][N:20]=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(C)([O-])C.[Na+]>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].C1(C)C=CC=CC=1>[Si:7]([O:6][CH2:5][C:4]1[C:3]([F:17])=[C:2]([N:28]2[CH2:29][CH2:30][N:25]([C:23]3[CH:22]=[CH:21][N:20]=[C:19]([CH3:18])[CH:24]=3)[CH2:26][CH2:27]2)[CH:16]=[CH:15][CH:14]=1)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]
参与物反应条件实验过程后处理来源与证据反应笔记

参与物

7

反应物 4

HCID 634876R-(+)-1,1'-联萘-2,2'-双二苯膦HCID 167623771-(2-甲基吡啶-4-基)哌嗪HCID 23676156叔丁醇钠HCID 86686195((3-Bromo-2-fluorobenzyl)oxy)(tert-butyl)dimethylsilane

产物 1

HCID 866862101-[3-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-4-(2-methylpyridin-4-yl)piperazine收率 66.3%

试剂、催化剂与溶剂 2

HCID 9811564三(二亚苄基丙酮)二钯催化剂
HCID 1140甲苯溶剂

反应条件

温度
80 °C

实验过程

[(3-Bromo-2-fluorobenzyl)oxy](tert-butyl)dimethylsilane (300 mg) was mixed with toluene (6 ml), and 1-(2-methylpyridin-4-yl)piperazine (200 mg), Pd2(dba)3 (43 mg), BINAP (88 mg), and sodium tert-butoxide (135 mg) were added thereto, followed by stirring at 80° C. for 5 hours. After cooling to room temperature, filtration was carried out by the addition of CHCl3 and Celite, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (EtOAc/hexane/28% aqueous ammonia/MeOH/) to obtain 1-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-4-(2-methylpyridin-4-yl)piperazine (259 mg).

后处理

  1. additionwere added
  2. temperatureAfter cooling to room temperature
  3. filtrationfiltration
  4. additionwas carried out by the addition of CHCl3 and Celite
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (EtOAc/hexane/28% aqueous ammonia/MeOH/)

来源与证据

ORD记录
ord-933a972618514b4a84f729dfafa2cdb9
来源数据集
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
专利号
US08716470B2

反应笔记

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本页导航参与物反应条件实验过程后处理来源与证据反应笔记