Methyl iodide → HCID 18799741, compound

HRID 1637733Notes

Reaction equation

HRID 1637733 reaction equation
[CH2:1]([Li])CCC.C(NC(C)C)(C)C.[Si:13]([O:20][C:21]1[CH:26]=[C:25]([O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[N:24]=[C:23]([S:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=2)[N:22]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].CI>O1CCCC1>[Si:13]([O:20][C:21]1[CH:26]=[C:25]([O:27][Si:28]([C:31]([CH3:33])([CH3:34])[CH3:32])([CH3:29])[CH3:30])[N:24]=[C:23]([S:35][CH:36]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=2)[CH3:1])[N:22]=1)([C:16]([CH3:17])([CH3:18])[CH3:19])([CH3:14])[CH3:15]

Participants

6

Reactant 4

HCID 6328Methyl iodide2×HCID 7912DiisopropylamineHCID 18799576HCID 18799576, compoundHCID 178418339Butyllithium

Product 1

HCID 18799741HCID 18799741, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

A solution of n-butyllithium (11.02 ml, 17.63 mmol, 1.2 equiv., 1.6 M in hexanes) in 60 ml of tetrahydrofuran cooled at -78° C. is treated dropwise with diisopropylamine (1.93 g, 19.10 mmol, 1.3 equiv.) over a two minute period. After stirring for another 10 min, a solution of 4,6-di-(tert-butyldimethylsilyloxy)-2-(2-pyridylmethyl)thio-pyrimidine (6.80 g, 14.69 mmol) in 16 ml of tetrahydrofuran is added dropwise over a 10 min period. The reaction mixture is stirred for 30 min longer and treated dropwise with methyl iodide (2.29 g, 16.16 mmol, 1.1 equiv.) in 6 ml of tetrahydrofuran over a 3 min period. Stirring is facilitated by adding an additional 30 ml of tetrahydrofuran. One hour after the addition of the methyl iodide, the cooling bath is removed and the mixture allowed to warm to room temperature. The contents are then cast into ice water and extracted once with ethyl acetate. The organic layer washed with saturated brine, dried with anhydrous Na2SO4 and concentrated at reduced pressure. A methylene chloride solution of the crude product was treated with silica gel (36 g), concentrated to a free flowing powder and applied to the top of a 350 g silica gel column, packed and eluted with ethyl acetate-hexane (5:95), to obtain 2.23 g (32%) 4,6-di-(tert-butyldimethylsilyloxy)-2-(1-(2-pyridyl)ethyl)thio-pyrimidine.

Workup

  1. stirringThe reaction mixture is stirred for 30 min longer
  2. stirringStirring
  3. customthe cooling bath is removed
  4. extractionextracted once with ethyl acetate
  5. washThe organic layer washed with saturated brine
  6. dry with materialdried with anhydrous Na2SO4
  7. concentrationconcentrated at reduced pressure
  8. additionA methylene chloride solution of the crude product was treated with silica gel (36 g)
  9. concentrationconcentrated to
  10. washeluted with ethyl acetate-hexane (5:95)

Sources & evidence

ORD record
ord-95bfc84bbda0497aa5573131222e0c44
Source dataset
uspto-grants-2000_03
Patent number
US06043248

Reaction notes

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