Trimethylsilylacetylene → 2-(Pyrimidin-4-yl)-4-(trimethylsilyl)but-3-yn-2-ol

HRID 1398527Notes

Reaction equation

HRID 1398527 reaction equation
C([Li])CCC.[C:6]([Si:8]([CH3:11])([CH3:10])[CH3:9])#[CH:7].[N:12]1[CH:17]=[CH:16][C:15]([C:18](=[O:20])[CH3:19])=[N:14][CH:13]=1>C1COCC1.O>[N:12]1[CH:17]=[CH:16][C:15]([C:18]([OH:20])([C:7]#[C:6][Si:8]([CH3:11])([CH3:10])[CH3:9])[CH3:19])=[N:14][CH:13]=1

Participants

6

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 5380601-(Pyrimidin-4-yl)ethanoneHCID 178418339Butyllithium

Product 1

HCID 681816232-(Pyrimidin-4-yl)-4-(trimethylsilyl)but-3-yn-2-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of n-butyllithium (2.5M in hexane, 2.1 ml, 5.32 mmol) in THF (3 mL) at −78° C. was added dropwise ethynyl(trimethyl)silane (0.7 mL, 4.91 mmol). The reaction was stirred at −78° C. for 10 minutes and then 1-(pyrimidin-4-yl)ethanone (0.5 g, 4.09 mmol) was added in more THF (2 mL). The reaction was stirred at −78° C. to RT overnight. The mixture was diluted with water and the volatiles removed in vacuo. The product was then extracted with CHCl3:IPA (2:1 ratio, 2×25 mL). The organic phase was washed with water (20 mL), brine (20 mL); dried over Na2SO4 and the solvent removed in vacuo. Purification by column chromatography (Biotage), eluting with 0-100% EtOAc-heptane afforded 2-(pyrimidin-4-yl)-4-(trimethylsilyl)but-3-yn-2-ol; 1H NMR (500 MHz, CDCl3) delta 0.19 (9H, s), 1.78 (3H, s), 4.65 (1H, s), 7.65 (1H, dd, J=5.20, 1.10 Hz), 8.79 (1H, d, J=5.36 Hz), 9.20 (1H, s); LC-MS: m/z=+221 (M+H)+; and 2-(pyrimidin-4-yl)but-3-yn-2-ol; 1H NMR (500 MHz, CDCl3) delta 1.79 (3H, s), 2.62 (1H, s), 4.99 (1H, s), 7.67 (1H, dd, J=5.28, 0.87 Hz), 8.77 (1H, d, J=5.36 Hz), 9.19 (1H, s); LC-MS: m/z=+148.95 (M+H)+.

Workup

  1. stirringThe reaction was stirred at −78° C. to RT overnight
  2. customthe volatiles removed in vacuo
  3. extractionThe product was then extracted with CHCl3:IPA (2:1 ratio, 2×25 mL)
  4. washThe organic phase was washed with water (20 mL), brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. customthe solvent removed in vacuo
  7. customPurification by column chromatography (Biotage)
  8. washeluting with 0-100% EtOAc-heptane

Sources & evidence

ORD record
ord-febca969b49448ebac1378ef73e997e1
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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