Piperidine → 1-{2-[4-(4-Bromo-thiophen-2-ylethynyl)-phenoxy]-ethyl}-pyrrolidine

HRID 1916730Notes

Reaction equation

HRID 1916730 reaction equation
N1CCCCC1.[Br:7][C:8]1[CH:9]=[C:10]([C:13]#[CH:14])[S:11][CH:12]=1.I[C:16]1[CH:29]=[CH:28][C:19]([O:20][CH2:21][CH2:22][N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:18][CH:17]=1>C1COCC1.[Cu]I>[Br:7][C:8]1[CH:9]=[C:10]([C:13]#[C:14][C:16]2[CH:29]=[CH:28][C:19]([O:20][CH2:21][CH2:22][N:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:18][CH:17]=2)[S:11][CH:12]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 219591661-(2-(4-Iodophenoxy)ethyl)pyrrolidineHCID 534266384-Bromo-2-ethynylthiophene2×

Product 1

HCID 673623061-{2-[4-(4-Bromo-thiophen-2-ylethynyl)-phenoxy]-ethyl}-pyrrolidine

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

Under an argon atmosphere 0.3 mL (3.13 mmol) piperidine, 14.9 mg (0.08 mmol) CuI and 90.3 mg (0.08 mmol) tetrakis-triphenylphosphane-palladium are added to a solution of 293 mg (1.56 mmol) 4-bromo-2-ethynyl-thiophene and 620 mg (1.56 mmol) 1-[2-(4-iodo-phenoxy)-ethyl]-pyrrolidine in 10 mL THF and the reaction mixture is stirred overnight at RT. To complete the reaction another 150 mg (0.8 mmol) 4-bromo-2-ethynyl-thiophene are added and the mixture is stirred for a further 24 h at RT. The mixture is evaporated down i. vac., the residue is triturated with EtOAc and the insoluble ingredients are filtered off. After the solvent has been eliminated the residue is purified by chromatography (silica gel, EtOAc/MeOH/NH3 8:2:0.2).

Workup

  1. additionare added
  2. stirringthe mixture is stirred for a further 24 h at RT
  3. customThe mixture is evaporated down i
  4. custom, the residue is triturated with EtOAc
  5. filtrationthe insoluble ingredients are filtered off
  6. customis purified by chromatography (silica gel, EtOAc/MeOH/NH3 8:2:0.2)

Sources & evidence

ORD record
ord-c96fea7864a94beb8b410c4ef128d374
Source dataset
uspto-grants-2013_12
Patent number
US08618132B2

Reaction notes

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