4-苄氧基溴苯 → (R)-4-(4-benzyloxyphenyl)-3-methylpiperazine-1-carboxylic acid tert-butyl ester

HRID 2172234

反应方程式

HRID 2172234 反应方程式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C@H:10]([CH3:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][C:26](Br)=[CH:25][CH:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.CC(C)([O-])C.[Na+].F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:26]2[CH:27]=[CH:28][C:23]([O:22][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:24][CH:25]=2)[C@H:10]([CH3:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参与物

9

反应物 4

HCID 1388354-苄氧基溴苯HCID 2756811(R)-4-Boc-2-甲基哌嗪HCID 23676156叔丁醇钠HCID 44558591Tri-t-butylphosphine fluoroborate

产物 1

HCID 70873375(R)-4-(4-benzyloxyphenyl)-3-methylpiperazine-1-carboxylic acid tert-butyl ester收率 92.2%

试剂、催化剂与溶剂 4

HCID 167845palladium acetate催化剂HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 1140甲苯溶剂HCID 8857乙酸乙酯溶剂

反应条件

温度
95 °C

实验过程

(3R)-1-tert-Butoxycarbonyl-3-methylpiperazine (3.0 g, 15.0 mmol), 4-benzyloxybromobenzene (4.73 g, 18.0 mmol), sodium tert-butoxide (2.02 g, 21.0 mmol) and toluene (30 ml) were mixed, and the atmosphere was replaced with nitrogen. tri-tert-Butylphosphine tetrafluoroborate (0.52 g, 1.8 mmol) and palladium acetate (0.34 g, 1.5 mmol) were added thereto and heated at 90 to 100° C. for 4 hours. Water and ethyl acetate were added to the brown reaction mixture, and insoluble matter was removed by filtration. The filtrate was separated into layers. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0→50:50) to afford the title compound as a colorless oil (5.29 g, 92%).

后处理

  1. customwas removed by filtration
  2. customThe filtrate was separated into layers
  3. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0→50:50)

来源与证据

ORD记录
ord-e1763bce0e2f411198f83df86f9a3817
来源数据集
uspto-grants-2015_06
专利号
US09051333B2

关联笔记

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