3-Hydroxybenzaldehyde → tert-Butyl4-{3-[2-(3-formylphenoxy)ethoxy]-2-pyrazinyl}-1-piperazinecarboxylate

HRID 353709노트

반응식

HRID 353709 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15]([O:20][CH2:21][CH2:22][OH:23])=[N:16][CH:17]=[CH:18][N:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=1)[CH:28]=[O:29].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH:28]([C:27]1[CH:26]=[C:25]([CH:32]=[CH:31][CH:30]=1)[O:23][CH2:22][CH2:21][O:20][C:15]1[C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)=[N:19][CH:18]=[CH:17][N:16]=1)=[O:29]

참가 물질

6

반응물 4

HCID 1013-Hydroxybenzaldehyde2회HCID 11776Triphenylphosphine2회HCID 220568ethyl N-ethoxycarbonyliminocarbamate2회HCID 114160742-[3-(4-Tert-butoxycarbonyl-1-piperazinyl)-2-pyrazinyloxy]ethanol2회

생성물 1

HCID 11304919tert-Butyl4-{3-[2-(3-formylphenoxy)ethoxy]-2-pyrazinyl}-1-piperazinecarboxylate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of the compound obtained in step 2 above (1.5 g, 4.7 mmol) in dry tetrahydrofuran (THF; 10 mL) was treated with 3-hydroxybenzaldehyde (0.74 g, 6.06 mmol) and triphenylphosphine (1.59 g, 6.06 mmol). This solution was stirred at room temperature then treated with diethyl azodicarboxylate (0.96 mL, 6.06 mmol) in dry THF (5 mL). After 1 hr, TLC indicated some remaining 2-[3-(4-tert-butoxycarbonyl-1-piperazinyl)-2-pyrazinyloxy]ethanol. The reaction was heated at reflux under nitrogen for 5 h, then left to cool to room temperature overnight. TLC again showed unreacted starter. The mixture was treated with further triphenylphosphine (0.80 g, 3.03 mmol), diethyl azodicarboxylate (0.5 mL, 3.03 mmol) and 3-hydroxybenzaldehyde (0.40 g, 3.03 mmol), then stirred at RT for a further 3 hrs (reaction complete by TLC). The volatiles were removed in vacuo and the residue was purified by flash column on silica gel, eluting with petroleum ether/ethyl acetate (2:1). This furnished 0.33 g (16%) of the title product as a colourless oil. 1H NMR (CDCl3) δ 1.5 (s, 9H); 3.5 (bs, 8H), 4.45 (m, 2H); 4.75 (m, 2H); 7.2 (d, 1H); 7.45 (s, 1H); 7.5 (m, 2H); 7.6 (s, 1H); 7.75 (s, 1H).

후처리

  1. temperatureThe reaction was heated
  2. temperatureat reflux under nitrogen for 5 h
  3. waitleft
  4. temperatureto cool to room temperature overnight
  5. stirringstirred at RT for a further 3 hrs
  6. custom(reaction complete by TLC)
  7. customThe volatiles were removed in vacuo
  8. customthe residue was purified by flash column on silica gel
  9. washeluting with petroleum ether/ethyl acetate (2:1)

출처 및 근거

ORD 기록
ord-445a969308dc4cee882c660b3fefc173
출처 데이터셋
uspto-grants-2004_06
특허 번호
US06756377B2

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