((1,1-Dimethyl-2-propynyl)oxy)trimethylsilane → 4-Methyl-1-(pyridin-4-yl)-4-(trimethylsilyloxy)pent-2-yn-1-one

HRID 655372Notes

Reaction equation

HRID 655372 reaction equation
[CH3:1][Si:2]([CH3:10])([CH3:9])[O:3][C:4]([CH3:8])([C:6]#[CH:7])[CH3:5].[Li]CCCC.CON(C)[C:19](=[O:26])[C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1>C1COCC1>[CH3:5][C:4]([O:3][Si:2]([CH3:10])([CH3:9])[CH3:1])([CH3:8])[C:6]#[C:7][C:19]([C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1)=[O:26]

Participants

5

Reactant 3

HCID 87344((1,1-Dimethyl-2-propynyl)oxy)trimethylsilaneHCID 3817473N-Methoxy-N-methylisonicotinamideHCID 178418339Butyllithium

Product 1

HCID 593547674-Methyl-1-(pyridin-4-yl)-4-(trimethylsilyloxy)pent-2-yn-1-oneYield 28.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a pre-cooled −78° C. stirred solution of trimethyl (2-methylbut-3-yn-2-yloxy) silane (5.0 g, 0.03 mol) in dry THF (150 mL), n-BuLi (23.82 mL, 0.03 mol, 1.6 M in hexane) was added dropwise over a period of 10 minutes under an inert atmosphere. The reactions was stirred for 30 minutes at −78° C. and then a solution of N-methoxy-N-methylisonicotinamide (6.34 g, 0.03 mol) in dry THF (30 mL) was added to the reaction mixture and stirring was continued for an additional 40 min at −78° C. The reaction mixture was quenched with a saturated NH4Cl solution and extracted with EtOAc (2×100 mL). The combined organic layers were washed with water (100 mL) and brine (100 mL), dried over Na2SO4, filtered and finally concentrated in vacuo to obtain a residue. The residue was purified via silica gel column chromatography eluting with 5% EtOAc in hexanes to afford 4-methyl-1-(pyridin-4-yl)-4-(trimethylsilyloxy) pent-2-yn-1-one (2.2 g, 27%) as oil.

Workup

  1. additionwas added dropwise over a period of 10 minutes under an inert atmosphere
  2. stirringstirring
  3. waitwas continued for an additional 40 min at −78° C
  4. customThe reaction mixture was quenched with a saturated NH4Cl solution
  5. extractionextracted with EtOAc (2×100 mL)
  6. washThe combined organic layers were washed with water (100 mL) and brine (100 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationfinally concentrated in vacuo
  10. customto obtain a residue
  11. customThe residue was purified via silica gel column chromatography
  12. washeluting with 5% EtOAc in hexanes

Sources & evidence

ORD record
ord-afd6778670c04fbfbac4d1ec2e55c603
Source dataset
uspto-grants-2011_12
Patent number
US08071595B2

Reaction notes

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