三氟乙酸 → 2-((6-Bromopyridin-2-yl)methyl)isoindoline-1,3-dione

HRID 17100

反应方程式

HRID 17100 反应方程式
[Br:1][C:2]1[N:7]=[C:6]([CH2:8]O)[CH:5]=[CH:4][CH:3]=1.[C:10]1(=[O:20])[NH:14][C:13](=[O:15])[C:12]2=[CH:16][CH:17]=[CH:18][CH:19]=[C:11]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(O)(C(F)(F)F)=O>O1CCCC1.O.CO>[Br:1][C:2]1[N:7]=[C:6]([CH2:8][N:14]2[C:10](=[O:20])[C:11]3[C:12](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:13]2=[O:15])[CH:5]=[CH:4][CH:3]=1

参与物

9

反应物 5

HCID 6422三氟乙酸2 次HCID 6809邻苯二甲酰亚胺HCID 11776三苯基膦HCID 73042偶氮二甲酰二哌啶HCID 35178116-溴吡啶-2-甲醇

产物 1

HCID 221764462-((6-Bromopyridin-2-yl)methyl)isoindoline-1,3-dione

试剂、催化剂与溶剂 3

HCID 887(5BETA,17BETA)-17-羟基-17-(甲基-D3)-2'H-雄甾-2-烯并[3,2-C]吡唑-5'(1'H)-酮溶剂3 次HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂2 次HCID 8028四氢呋喃溶剂

实验过程

A mixture of commercially available (6-bromopyridin-2-yl)methanol (20.0 g, 0.106 mol), phthalimide (20.4 g, 0.138 mol), and triphenylphosphine (36.2 g, 0.138 mol), and 1,1′-(azodicarbonyl)-dipiperidine (34.8 g, 0.138 mol) in anhydrous tetrahydrofuran (1 L) was stirred at room temperature overnight. The precipitate was collected by vacuum filtration and washed with tetrahydrofuran. The filtrate was concentrated under reduced pressure, and the solid residue was triturated with methanol with sonication. A214.1 was collected by vacuum filtration and was dried well to give 24.1 g as a white solid. The filtrate still contained significant product which could be isolated as a second crop with methanol trituration. The compound had an HPLC retention time=2.32 min. (Column: Chromolith SpeedROD 4.6×50 mm—4 min.; Solvent A=10% MeOH, 90% H2O, and 0.1% TFA; Solvent B=90% MeOH, 10% H2O, and 0.1% TFA) and a LC/MS M+1=317.15 and 319.15.

后处理

  1. filtrationThe precipitate was collected by vacuum filtration
  2. washwashed with tetrahydrofuran
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customthe solid residue was triturated with methanol with sonication
  5. filtrationA214.1 was collected by vacuum filtration
  6. customwas dried well
  7. customto give 24.1 g as a white solid

来源与证据

ORD记录
ord-b3467d2092bb4e8c87455c945af69572
来源数据集
uspto-grants-2010_06
专利号
US07737279B2

关联笔记

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