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

HRID 80915Notes

Reaction equation

HRID 80915 reaction equation
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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

[(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.

Workup

  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.)

Sources & evidence

ORD record
ord-7ca887fedbb744818fe412aba752d0e9
Source dataset
uspto-grants-2014_09
Patent number
US08846677B2

Reaction notes

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