Potassium Carbonate → tert-Butyl 4-((6-chloropyridin-3-yl)methyl)piperazine-1-carboxylate

HRID 79201

Reaction equation

HRID 79201 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8]Cl)=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[N:16]1([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.[OH-].[Na+]>C(#N)C>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([CH2:8][N:19]2[CH2:18][CH2:17][N:16]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 1554792-Chloro-5-(chloromethyl)pyridine

Product 1

HCID 45788993tert-Butyl 4-((6-chloropyridin-3-yl)methyl)piperazine-1-carboxylateYield 84.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred suspension of 2-chloro-5-(chloromethyl)pyridine (2.0 g, 12 mmol) in acetonitrile (40 mL) was added potassium carbonate (1.5 mL, 25 mmol) followed by tert-butyl 1-piperazinecarboxylate (2.3 g, 12 mmol). The resulting mixture was stirred at room temperature for 20 h. Upon workup, the mixture was poured into ice and 2 N NaOH aqueous solution and extracted with ethyl acetate (2×). The combined organics were dried over Na2SO4 and concentrated in vacuo. The residue was subjected to combi-flash column chromatography (methanol/DCM) to give compound 339 (3.17 g, 82% yield) as a thick colorless liquid. 1H NMR 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.32 (1 H, d, J=2.0 Hz), 7.66 (1 H, d, J=7.4 Hz), 7.30 (1 H, d, J=8.2 Hz), 3.50 (2 H, s), 3.37-3.47 (4 H, m), 2.38 (4 H, br. s.), 1.46 (9 H, s). LCMS-ESI (POS), M/Z, M+1: Found 312.1.

Workup

  1. extractionextracted with ethyl acetate (2×)
  2. dry with materialThe combined organics were dried over Na2SO4
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-11d42e68f9ba40d8850ba8553b1c370c
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Linked notes

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