Water → 1-(5-Bromopyridin-2-yl)-4-cyclopropylpiperazine

HRID 80915노트

반응식

HRID 80915 반응식
C(O[C:4]1(O[Si](C)(C)C)[CH2:6][CH2:5]1)C.[Br:12][C:13]1[CH:14]=[CH:15][C:16]([N:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[N:17][CH:18]=1.O.[BH3-]C#N.[Na+]>C1COCC1.C(O)(=O)C>[Br:12][C:13]1[CH:14]=[CH:15][C:16]([N:19]2[CH2:20][CH2:21][N:22]([CH:4]3[CH2:5][CH2:6]3)[CH2:23][CH2:24]2)=[N:17][CH:18]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 164142271-(5-Bromopyridin-2-yl)piperazine

생성물 1

HCID 231545451-(5-Bromopyridin-2-yl)-4-cyclopropylpiperazine

시약·촉매·용매 2

HCID 176Acetic Acid용매HCID 8028Tetrahydrofuran용매2회

실험 절차

[(1-Ethoxy-cyclopropyl)oxy]trimethylsilane (26 mL, 129.3 mmol) was added to a solution of 1-(5-bromopyridin-2-yl)-piperazine (15 g, 62.0 mmol) in THF (120 mL). Water (24 mL), acetic acid (11 mL), and 1 M NaCNBH3 in THF (90 mL, 90 mmol) were added to the reaction mixture, which was then heated at reflux temperature for 3 hours. The resulting solution was cooled to rt and evaporated to dryness in vacuo. The residue was dissolved in a mixture of dichloromethane (200 mL) and water (50 mL) and 4 N sodium hydroxide (20 mL) was added to pH 8-9. The organic phase was isolated and the aqeoues phase was extracted with further dichloromethane (100 mL). The combined organic phases were evaporated to dryness in vacuo and the residue was purified on a silica gel column (gradient: from 5% ethyl acetate in heptane to 100% ethyl acetate over 40 min.). This afforded 13.1 g (75%) of 1-(5-bromopyridin-2-yl)-4-cyclopropylpiperazine.

후처리

  1. temperaturewas then heated
  2. temperatureat reflux temperature for 3 hours
  3. customevaporated to dryness in vacuo
  4. dissolutionThe residue was dissolved in a mixture of dichloromethane (200 mL) and water (50 mL) and 4 N sodium hydroxide (20 mL)
  5. additionwas added to pH 8-9
  6. customThe organic phase was isolated
  7. extractionthe aqeoues phase was extracted with further dichloromethane (100 mL)
  8. customThe combined organic phases were evaporated to dryness in vacuo
  9. customthe residue was purified on a silica gel column (gradient: from 5% ethyl acetate in heptane to 100% ethyl acetate over 40 min.)

출처 및 근거

ORD 기록
ord-7ca887fedbb744818fe412aba752d0e9
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846677B2

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