Tetrahydrofuran → 2-(4-Chloro-thiophen-2-yl)-6-methyl-pyridine

HRID 1432623Notes

Reaction equation

HRID 1432623 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([Cl:7])[CH:6]=1.[Br-].[CH3:9][C:10]1[N:15]=[C:14]([Zn+])[CH:13]=[CH:12][CH:11]=1.C1COCC1>CCOCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:7][C:5]1[CH:6]=[C:2]([C:14]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:9])[N:15]=2)[S:3][CH:4]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 137808382-Bromo-4-chlorothiopheneHCID 178426002HCID 178426002, compound

Product 1

HCID 688400882-(4-Chloro-thiophen-2-yl)-6-methyl-pyridineYield 28%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 2-bromo-4-chloro-thiophene (Gronowitz, Rosén Chemica Scripta, 1971, 1, 33) (1.50 g, 7.60 mmol) and 0.5 M solution of 6-methyl-2-pyridylzinc bromide in THF (23.00 mL, 11.39 mmol) is added Pd(PPh3)4 (0.18 g, 0.15 mmol). The solution is heated at 40° C. overnight, diluted with Et2O (50 mL), washed with sat. NH4Cl (40 mL), dried over MgSO4, filtered on concentrated. The residue is purified by ISCO column chromatography (5%-20% EtOAc/hexane gradient) furnish the title compound (0.45 g, 2.15 mmol, 28%). 1H NMR (CDCl3), δ 2.56 (s, 3H), 7.02 (d, 7.7 Hz, 1H), 7.13 (d, J=0.9 Hz, 1H), 7.36 (d, J=7.9 Hz, 1H), 7.39 (d, J=0.9 Hz, 1H), 7.54 (dd, J=7.9, 7.7, 1H).

Workup

  1. washwashed with sat. NH4Cl (40 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationon concentrated
  5. customThe residue is purified by ISCO column chromatography (5%-20% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-c389d7d85a6549479abb62a3329f701c
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

Loading…