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

HRID 1158228Notes

Reaction equation

HRID 1158228 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-371f6eb4e8804e809b43b1e296acfbb9
Source dataset
uspto-grants-2010_10
Patent number
US07807832B2

Reaction notes

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