Nitrogen → 2-Chloro-4-(2-(trimethylsilyl)ethynyl)pyrimidine

HRID 885633Notes

Reaction equation

HRID 885633 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.N#N.[CH3:11][Si:12]([C:15]#[CH:16])([CH3:14])[CH3:13]>C1COCC1.CCN(CC)CC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:16]#[C:15][Si:12]([CH3:14])([CH3:13])[CH3:11])[CH:5]=[CH:4][N:3]=1

Participants

8

Reactant 3

HCID 947NitrogenHCID 66111TrimethylsilylacetyleneHCID 775312,4-Dichloropyrimidine

Product 1

HCID 115720232-Chloro-4-(2-(trimethylsilyl)ethynyl)pyrimidineYield 86.6%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of Pd(PPh3)2Cl2 (0.9 g) and PPh3 (0.7 g) in THF (200 mL) and Et3N (300 mL) was added 2,4-dichloropyrimidine (40 g, 0.27 mol) under a stream of N2. After bubbling N2 into the solution for 15 min, CuI (0.5 g) was added, followed by (trimethylsilyl)acetylene (29 g, 0.29 mol). The mixture was heated at reflux for 4.5 h. The mixture was cooled to rt and filtered, washing with EtOAc. The filtrated was concentrated and the residue was diluted with hexanes (500 mL) and loaded directly onto a short pad of SiO2. The product was eluted with 10% EtOAc/hexanes to provide a light orange solid (49.3 g), which was used without further purification. TLC: Rf=0.42. mp 51-54° C. IR: 3125 (w), 2961 (w), 1557 (s), 1523 (s). 1H NMR: 8.58 (d, J=5.0 Hz, 1H), 7.30 (d, J=5.0 Hz, 1H), 0.28 (s, 9H). 13C NMR: 162.23, 160.16, 153.41, 122.52, 104.23, 100.75, 0.01. Anal. Calcd for C9H11ClN2Si: C, 51.29; H, 5.26; N, 13.29. Found: C, 51.45; H, 5.16; N, 13.33.

Workup

  1. customAfter bubbling N2 into the solution for 15 min
  2. additionCuI (0.5 g) was added
  3. temperatureThe mixture was heated
  4. temperatureat reflux for 4.5 h
  5. filtrationfiltered
  6. washwashing with EtOAc
  7. concentrationThe filtrated was concentrated
  8. additionthe residue was diluted with hexanes (500 mL)
  9. washThe product was eluted with 10% EtOAc/hexanes

Sources & evidence

ORD record
ord-435047e3147b4af78aec644538b6674b
Source dataset
uspto-grants-2012_08
Patent number
US08242273B2

Reaction notes

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