Triethylamine → 4-(2,5-Dichloro-pyridin-4-ylethynyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1471766Notes

Reaction equation

HRID 1471766 reaction equation
C(N(CC)CC)C.[Cl:8][C:9]1[CH:14]=[C:13](I)[C:12]([Cl:16])=[CH:11][N:10]=1.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH:27]([C:30]#[CH:31])[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18]>CN(C)C=O.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH:27]([C:30]#[C:31][C:13]2[C:12]([Cl:16])=[CH:11][N:10]=[C:9]([Cl:8])[CH:14]=2)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 15550481tert-Butyl 4-ethynylpiperidine-1-carboxylateHCID 534009652,5-Dichloro-4-iodopyridine

Product 1

HCID 866748934-(2,5-Dichloro-pyridin-4-ylethynyl)-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Copper(I) iodide (0.50 g), bis-(triphenylphosphine)-palladium(II) chloride (0.50 g), and triethylamine (3.4 mL) are added successively to a solution of 2,5-dichloro-4-iodo-pyridine (6.54 g) in N,N-dimethylformamide (45 mL) under Ar atmosphere at room temperature. The resulting mixture is stirred at room temperature for 1 h prior to the addition of 4-ethynyl-piperidine-1-carboxylic acid tert-butyl ester (5.15 g). The mixture is stirred at 55° C. for 2 h. The solvent is evaporated and the residue is diluted with ethyl acetate. The resulting mixture is washed with water and brine, dried (Na2SO4), and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 85:15→50:50) to give the title compound. LC (method 3): tR=1.66 min; Mass spectrum (ESI+): m/z=355/357/359 (2 Cl) [M+H]+.

Workup

  1. stirringThe mixture is stirred at 55° C. for 2 h
  2. customThe solvent is evaporated
  3. additionthe residue is diluted with ethyl acetate
  4. washThe resulting mixture is washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 85:15→50:50)

Sources & evidence

ORD record
ord-bf914f24bc3f4b338d371eb5e08466db
Source dataset
uspto-grants-2015_04
Patent number
US09012456B2

Reaction notes

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