Toluene → 3-(1-((tert-butyldimethylsilyl)oxy)ethyl)-4-(pyridin-2-yl)-1H-isochromen-1-one

HRID 634376Notes

Reaction equation

HRID 634376 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[O:4][C:3]=1[CH:13]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH3:14].C1(C)C=CC=CC=1.C([Sn](CCCC)(CCCC)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=1)CCC>>[Si:16]([O:15][CH:13]([C:3]1[O:4][C:5](=[O:12])[C:6]2[C:11]([C:2]=1[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH3:14])([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]

Participants

4

Reactant 3

HCID 1140TolueneHCID 6077842-(Tributylstannyl)pyridineHCID 1239597364-bromo-3-(1-((tert-butyldimethylsilyl)oxy)ethyl)-1H-isochromen-1-one2×

Product 1

HCID 1239811473-(1-((tert-butyldimethylsilyl)oxy)ethyl)-4-(pyridin-2-yl)-1H-isochromen-1-one

Procedure

To a degassed solution of 4-bromo-3-(1-((tert-butyldimethylsilyl)oxy)ethyl)-1H-isochromen-1-one (intermediate A8, 2 g, 5.22 mmol) in toluene (30 ml) PdCl2(PPh3)2 (0.183 g, 0.261 mmol) was added followed by 2-(tributylstannyl)pyridine (4.55 ml, 10.44 mmol) and the resulting mixture was heated to reflux overnight. The mixture was allowed to cool to RT and then and filtered through a celite pad. The solvent was removed in vacuo, the crude was dissolved in AcOEt and an aqueous sat. sol of KF was added and the mixture was stirred for 2 hrs. The organic phase was separated, dried over sodium sulfate and evaporated to dryness. The crude was purified by flash chromatography on silica gel Biotage cartridge (cyclohexane to cyclohexane:EtOAc=20:80) to afford 3-(1-((tert-butyldimethylsilyl)oxy)ethyl)-4-(pyridin-2-yl)-1H-isochromen-1-one as a pale yellow oil (Intermediate B58.1, 0.508 g, 1.33 mmol).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux overnight
  3. filtrationfiltered through a celite pad
  4. customThe solvent was removed in vacuo
  5. dissolutionthe crude was dissolved in AcOEt
  6. additionan aqueous sat. sol of KF was added
  7. customThe organic phase was separated
  8. dry with materialdried over sodium sulfate
  9. customevaporated to dryness
  10. customThe crude was purified by flash chromatography on silica gel Biotage cartridge (cyclohexane to cyclohexane:EtOAc=20:80)

Sources & evidence

ORD record
ord-96049d931c4a4382bf230cc1ad9f9f7d
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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