2-Bromo-6-methylpyridine → 2-(5-Bromo-4-methyl-thiophen-2-yl)-6-methyl-pyridine

HRID 1639661Notes

Reaction equation

HRID 1639661 reaction equation
C([N-]C(C)C)(C)C.[Li+].[Br:9][C:10]1[S:11][CH:12]=[CH:13][C:14]=1[CH3:15].Br[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[N:18]=1>[Cl-].[Cl-].[Zn+2].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.C1COCC1>[Br:9][C:10]1[S:11][C:12]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[N:18]=2)=[CH:13][C:14]=1[CH3:15]

Participants

7

Reactant 3

HCID 792052-Bromo-6-methylpyridineHCID 843142-Bromo-3-methylthiopheneHCID 2724682Lithium diisopropylamide

Product 1

HCID 667211492-(5-Bromo-4-methyl-thiophen-2-yl)-6-methyl-pyridineYield 49.2%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Add 2.0 M lithium diisopropylamide (9.76 mL, 19.52 mmol) to a −78° C. solution of 2-bromo-3-methyl-thiophene (2.0 mL, 17.75 mmol) and THF (30 mL). After 45 minutes add ZnCl2 (0.5 M in THF, 39.0 mL, 19.50 mmol) and stir the solution for 30 min. Add 2-bromo-6-methyl-pyridine (2.4 mL, 21.29 mmol) and Pd(PPh3)4 (0.50 g, 0.44 mmol). Warm the solution to ambient temperature and stir for 2 h. Wash the reaction with saturated NH4Cl solution (20 mL). Wash the aqueous layer with CH2Cl2 (30 mL). Combine the organic layers, wash with saturated NH4Cl solution (20 mL), dry over Na2SO4, filter and concentrate. Purify the resulting residue by silica gel column chromatography (10%-20% EtOAc/hexane gradient) to furnish the title compound (2.34 g, 49%). LC-ES/MS m/z (79Br/81Br) 267.7/269.5 (M+H)+.

Workup

  1. stirringstir for 2 h
  2. washWash
  3. customthe reaction with saturated NH4Cl solution (20 mL)
  4. washWash the aqueous layer with CH2Cl2 (30 mL)
  5. washCombine the organic layers, wash with saturated NH4Cl solution (20 mL)
  6. dry with materialdry over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate
  9. customPurify the resulting residue by silica gel column chromatography (10%-20% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-5e68308314fb4f7eac402d1b76d3854b
Source dataset
uspto-grants-2012_02
Patent number
US08110580B2

Reaction notes

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