Dimethylformamide → 2-Benzyl-piperazine-1,2,4-tricarboxylic acid 1-benzyl ester 4-tert-butyl ester 2-methyl ester

HRID 636831

反応式

HRID 636831 の反応式
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8][CH2:7][N:6]1[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])=[O:4].CN(C)C=O.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:43](Br)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1([CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:15])[CH3:16])=[O:12])[CH2:8][CH2:7][N:6]1[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])=[O:4]

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 44519651-Benzyl 4-tert-butyl 2-methyl piperazine-1,2,4-tricarboxylate

生成物 1

HCID 536928572-Benzyl-piperazine-1,2,4-tricarboxylic acid 1-benzyl ester 4-tert-butyl ester 2-methyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To a stirred solution of piperazine-1,2,4-tricarboxylic acid 1-benzyl ester 4-tert-butyl ester 2-methyl ester (20.0 g, 53 mmol) in tetrahydrofuran (500 mL) under nitrogen was added N,N-dimethylformamide (50 mL). The reaction was cooled to about −78° C., and a 1 M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (80 mL) was added. The reaction was stirred at about −78° C. for about 1 hour, and then benzyl bromide (9.4 mL, 79 mmol) was added. The reaction was stirred for about 30 minutes more at about −78° C., then warmed to room temperature and stirred overnight. The reaction was quenched with saturated sodium bicarbonate solution, and the mixture was extracted three times with ethyl acetate. The combined organic layers were extracted twice with water, brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give 31 g of crude product. Purification by silica gel chromatography using 10-20% ethyl acetate/hexanes as eluent afforded the title compound of part 4-A (20.3 g, 82%): +APcI MS (M−tBu+H)+ 413, (M−Boc+H)+ 369; 1H NMR=400 MHz (CDCl3) δ: 7.37 (arom, m, 5H), 7.22 (arom, m, 3H), 7.00 (arom, m, 2H), 1.41 (BOC, d, 9H).

後処理

  1. stirringThe reaction was stirred for about 30 minutes more at about −78° C.
  2. temperaturewarmed to room temperature
  3. stirringstirred overnight
  4. customThe reaction was quenched with saturated sodium bicarbonate solution
  5. extractionthe mixture was extracted three times with ethyl acetate
  6. extractionThe combined organic layers were extracted twice with water, brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give 31 g of crude product
  11. customPurification by silica gel chromatography

出典と根拠

ORDレコード
ord-d3c9e9ed2ef04e6f927f567860022033
出典データセット
uspto-grants-2001_02
特許番号
US06194578B1

関連ノート

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