Acetic Acid → 1-[(6-Chloropyridin-3-yl)methyl]-4-methylpiperazine

HRID 402931Notes

Reaction equation

HRID 402931 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][N:3]=1.[CH3:10][N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([CH2:6][N:14]2[CH2:15][CH2:16][N:11]([CH3:10])[CH2:12][CH2:13]2)=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 27640536-Chloropyridine-3-carbaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 14735211-[(6-Chloropyridin-3-yl)methyl]-4-methylpiperazineYield 85.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

In a 500 ml round bottom flask 6-chloronicotinaldehyde (5 g, 35.3 mmol, Eq: 1.00) was suspended in DCM (350 ml). 1-Methylpiperazine (4.42 g, 4.9 ml, 44.2 mmol, Eq: 1.25) was added, followed by acetic acid (4.24 g, 4.04 ml, 70.6 mmol, eq: 2.0). Sodium triacetoxyborohydride (11.2 g, 53.0 mmol, Eq: 1.5) was added by portions over several minutes. The reaction stirred at room temperature for three hours. Water and DCM were added and the layers were separated. The aqueous layer was brought to pH 10 with 1M NaOH. The aqueous layer was extracted three times with DCM. The combined extract was dried over Na2SO4 and concentrated in vacuo to give 1-(6-chloro-pyridin-3-ylmethyl)-4-methyl-piperazine (6.8 g, 85%) LC/MS-ESI observed [M+H]+ 226. The crude material was used “as is” in the next reaction.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted three times with DCM
  3. extractionThe combined extract
  4. dry with materialwas dried over Na2SO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b0a5df02f4b547f9ac7de9e7fb3a316a
Source dataset
uspto-grants-2014_06
Patent number
US08742098B2

Reaction notes

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