Methyl iodide → 2-Bromo-6-ethylpyridine

HRID 2079749Notes

Reaction equation

HRID 2079749 reaction equation
[CH2:1]([Li])CCC.C(NC(C)C)(C)C.C(=O)=O.CC(C)=O.[Br:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[N:22]=1.CI>O1CCCC1.O>[Br:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][CH3:1])[N:22]=1

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 792052-Bromo-6-methylpyridineHCID 18522661Acetone cardiceHCID 178418339Butyllithium

Product 1

HCID 129548002-Bromo-6-ethylpyridineYield 75%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Add under nitrogen a solution of 2.5; M n-butyllithium in hexanes (186.74; mL, 0.467; mol) over 41; min to a solution of diisopropylamine (68.7; mL, 0.488; mol) in tetrahydrofuran (745; mL, 9.16; mol) at −78° C. (dry-ice/acetone bath). Stir for 15; min and add 2-bromo-6-methylpyridine (49.3; mL, 0.424; mol) dropwise over 22; min. Stir 15; min, add methyl iodide (52.87; mL, 0.848; mol) dropwise over 1; hour and then warm to room temperature over 1.5; hour. Add water (250; mL) while cooling with a dry-ice/acetone bath and separate the layers. Extract the aqueous phase twice with ethyl acetate (300 mL). Combine the organic phases, concentrate and purify by silica gel chromatography, gradient eluting from 100:0; to 80:20; using hexanes:ethyl acetate, to give the title compound as a yellow oil (59.74; g, 75%). 1H NMR (CDCl3) δ 1.28; (t, 3H), 2.80; (q, 2H), 7.11; (d, 1H), 7.27; (d, 1H), 7.45; (t, 1H).

Workup

  1. additionAdd under nitrogen a solution of 2.5
  2. customat −78° C.
  3. stirringStir 15
  4. customseparate the layers
  5. extractionExtract the aqueous phase twice with ethyl acetate (300 mL)
  6. concentrationCombine the organic phases, concentrate
  7. custompurify by silica gel chromatography
  8. washgradient eluting from 100:0

Sources & evidence

ORD record
ord-b815e50164614c0182e529eaf39064bd
Source dataset
uspto-grants-2011_04
Patent number
US07932274B2

Reaction notes

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