N-Methoxy-N-methylisonicotinamide → 1-(Pyridin-4-yl)-3-(1-(trimethylsilyloxy)cyclopentyl)prop-2-yn-1-one

HRID 1258349Notes

Reaction equation

HRID 1258349 reaction equation
[C:1]([C:3]1([O:8][Si:9]([CH3:12])([CH3:11])[CH3:10])[CH2:7][CH2:6][CH2:5][CH2:4]1)#[CH:2].[Li]CCCC.CON(C)[C:21](=[O:28])[C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1>C1COCC1>[N:25]1[CH:26]=[CH:27][C:22]([C:21](=[O:28])[C:2]#[C:1][C:3]2([O:8][Si:9]([CH3:10])([CH3:12])[CH3:11])[CH2:7][CH2:6][CH2:5][CH2:4]2)=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 3817473N-Methoxy-N-methylisonicotinamideHCID 15396659[(1-Ethynylcyclopentyl)oxy](trimethyl)silaneHCID 178418339Butyllithium

Product 1

HCID 593548151-(Pyridin-4-yl)-3-(1-(trimethylsilyloxy)cyclopentyl)prop-2-yn-1-oneYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of (1-ethynylcyclopentyloxy)trimethylsilane (2.0 g, 11.0 mmol) in dry THF (50 mL) was added n-BuLi (20.0 mL, 20.0 mmol, 1.6 M in hexane) drop wise at −78° C. under an inert atmosphere for a period of 10 min. After being stirred for 30 min at −78° C., a solution of compound N-methoxy-N-methylisonicotinamide (2.1 g, 13.2 mmol) in dry THF (10 mL) was added to the reaction mixture and stirring was continued for an additional 2 h at −78° C. The reaction mixture was quenched with a saturated NH4Cl solution and extracted with EtOAc (2×60 mL). The combined organic layers were washed with water (20 mL), brine (20 mL), dried over Na2SO4, filtered and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography eluting with 5% EtOAc in Hexane to afford 1-(pyridin-4-yl)-3-(1-(trimethylsilyloxy)cyclopentyl)prop-2-yn-1-one (1.0 g, 32%) as an oil.

Workup

  1. stirringstirring
  2. waitwas continued for an additional 2 h at −78° C
  3. customThe reaction mixture was quenched with a saturated NH4Cl solution
  4. extractionextracted with EtOAc (2×60 mL)
  5. washThe combined organic layers were washed with water (20 mL), brine (20 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto obtain the crude product
  10. customThe crude material was purified via silica gel column chromatography
  11. washeluting with 5% EtOAc in Hexane

Sources & evidence

ORD record
ord-b211c6687b994af8bf0a68307c974501
Source dataset
uspto-grants-2013_06
Patent number
US08466148B2

Reaction notes

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