Trimethylsilylacetylene → 4-Ethynyl-2-(methylthio)pyrimidine

HRID 925421Notes

Reaction equation

HRID 925421 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([S:8][CH3:9])[N:3]=1.C[Si]([C:14]#[CH:15])(C)C>C1COCC1.[Cu]I.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:14]([C:2]1[CH:7]=[CH:6][N:5]=[C:4]([S:8][CH3:9])[N:3]=1)#[CH:15]

Participants

7

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 971134-Chloro-2-methylthiopyrimidine

Product 1

HCID 179654774-Ethynyl-2-(methylthio)pyrimidineYield 53.3%

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneCatalystHCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Pd(PPh3).CH2Cl2 (22 mg, 0.031 mmol) and PPh3 (17 mg, 0.065 mmol) in THF (200 mL), TEA (300 mL), and 4-Chloro-2-methylsulfanyl-pyrimidine (1.0 g, 6.75 mmol, 1 eq.) were added under argon. CuI (13 mg, 0.065 mmol) and trimethylsilylacetylene (725 mg, 7.25 mmol, 1.1 eq) were then added sequentially. The reaction mixture was heated at reflux for 8 h and cooled to rt. The precipitate was filtered off and washed with AcOEt. The filtrate solution was concentrated and the residue was diluted with DCM and 3 g of silica gel. The solvent was removed and the residue was loaded on silica column. The product was eluted with 10% AcOEt/hexanes to provide the desilylated product (540 mg, 3.6 mmol, 53%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 8 h
  3. filtrationThe precipitate was filtered off
  4. washwashed with AcOEt
  5. concentrationThe filtrate solution was concentrated
  6. additionthe residue was diluted with DCM and 3 g of silica gel
  7. customThe solvent was removed
  8. washThe product was eluted with 10% AcOEt/hexanes

Sources & evidence

ORD record
ord-d62f000a70344662bc93b4f2896d5b69
Source dataset
uspto-grants-2016_03
Patent number
US09284298B2

Reaction notes

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