Toluene → HCID 54505552, 화합물

HRID 636830

반응식

HRID 636830 반응식
[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].C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.[F:45][C:46]1[CH:53]=[CH:52][C:49]([CH2:50]Br)=[CH:48][CH:47]=1>O1CCCC1.CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1([CH2:50][C:49]2[CH:52]=[CH:53][C:46]([F:45])=[CH:47][CH:48]=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]

참가 물질

7

반응물 4

HCID 1140TolueneHCID 680214-Fluorobenzyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 44519651-Benzyl 4-tert-butyl 2-methyl piperazine-1,2,4-tricarboxylate

생성물 1

HCID 54505552HCID 54505552, 화합물

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

To a stirred solution of piperazine-1,2,4-tricarboxylic acid 1-benzyl ester 4-tert-butyl ester 2-methyl ester (10.5 g, 27.8 mmol), prepared as described by Bigge et al. (Tetrahedron Let. 1989, 30, 5193), in tetrahydrofuran (200 mL) under a nitrogen atmosphere was added N,N-dimethylformamide (30 mL). The reaction was cooled to about −78° C., and a 0.5 M solution of potassium bis(trimethylsilyl)amide in toluene (83 mL, 42 mmol) was added. The reaction was stirred at about −78° C. for about 1 hour, and then 4-fluorobenzyl bromide (5.2 mL, 42 mmol) was added. The reaction was stirred for about 1 hour 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 the crude product as a yellow oil. Purification by silica gel chromatography using 0-20% ethyl acetate/hexanes as eluent afforded the title compound of part 1-A (8.54 g, 63%) as a colorless oil: +APcI MS (M−Boc+H)+ 387; 1H NMR=400 MHz (CDCL3) δ: 7.45-7.30 (arom, br s, 5H), 7.00-6.80 (arom, br m, 4H), 5.35-5.05 (br m, 2H), 2.53 (br t, 1H), 1.40 (Boc, s, 9H).

후처리

  1. stirringThe reaction was stirred for about 1 hour 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 the crude product as a yellow oil
  11. customPurification by silica gel chromatography

출처 및 근거

ORD 기록
ord-5e588bb12b574a7abf3ae99bcbf219f4
출처 데이터셋
uspto-grants-2001_02
특허 번호
US06194578B1

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