Methyl iodide → Lithium diisopropylamide

HRID 2380041Notes

Reaction equation

HRID 2380041 reaction equation
[CH:1]([NH:4][CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].[CH2:8]([Li:12])CCC.[CH2:13]([C:15]1[CH:20]=[CH:19][N:18]=[CH:17][N:16]=1)[CH3:14].IC>CCCCCC.O1CCCC1.O>[CH:1]([N-:4][CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].[Li+:12].[CH3:14][CH:13]([C:15]1[CH:20]=[CH:19][N:18]=[CH:17][N:16]=1)[CH3:8]

Participants

9

Reactant 4

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 110078414-EthylpyrimidineHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 189565064-Isopropylpyrimidine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

A solution of lithium diisopropylamide was prepared as described in Example 1(i) from diisopropylamine (6.88 g) and n-butyllithium (27.0 ml of a 2.5M solution in hexane) in dry tetrahydrofuran (180 ml) under an atmosphere of dry nitrogen. To this solution at -70° , a solution of 4-ethylpyrimidine (7.35 g) in dry tetrahydrofuran (20 ml) was added dropwise over 0.17 hour. The solution was stirred at -70° for 0.75 hour and then iodomethane (11.60 g) was added. The mixture was stirred for a further 3 hours and then warmed to room temperature. Water was added and the solution was evaporated to low bulk, then partitioned between ethyl acetate and water. The organic layer was separated, the aqueous layer was extracted three times with ethyl acetate and the organic fractions were combined and dried (Na2SO4). Evaporation of the solvent gave an oil which was chromatographed on silica gel, using dichloromethane/ether (9:1) as eluant. The fractions containing the product were combined and evaporated, and the residual oil was distilled to give the title compound, (3.14 g), b.p. 52°-56° at 15 mm.

Workup

  1. stirringThe mixture was stirred for a further 3 hours
  2. customthe solution was evaporated to low bulk
  3. custompartitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted three times with ethyl acetate
  6. dry with materialdried (Na2SO4)
  7. customEvaporation of the solvent
  8. customgave an oil which
  9. customwas chromatographed on silica gel
  10. additionThe fractions containing the product
  11. customevaporated
  12. distillationthe residual oil was distilled

Sources & evidence

ORD record
ord-3df6802ddc3644a6aca0f3e4b9dd54e2
Source dataset
uspto-grants-1994_11
Patent number
US05364938

Reaction notes

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