Benzyl acetate → 1-(2-Methylsulfanyl-pyrimidin-4-yl)-propan-2-one

HRID 2359760Notes

Reaction equation

HRID 2359760 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([S:8][CH3:9])[N:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:20](OCC1C=CC=CC=1)(=[O:22])[CH3:21]>C1COCC1>[CH3:9][S:8][C:4]1[N:3]=[C:2]([CH2:1][C:20](=[O:22])[CH3:21])[CH:7]=[CH:6][N:5]=1

Participants

5

Reactant 3

HCID 8785Benzyl acetateHCID 8212614-Methyl-2-(methylsulfanyl)pyrimidineHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 596066061-(2-Methylsulfanyl-pyrimidin-4-yl)-propan-2-oneYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-Methyl-2-(methylthio)pyrimidine (1) (3 g, 21.40 mmol) in THF (35.7 mL) at −10° C. was added LHMDS (32.1 mL, 32.1 mmol, 1M in THF). The resulting reaction was warmed to rt and stirred for 15 minutes, after which time the reaction was cooled back to −10° C. and Benzyl Acetate (3.21 mL, 23.54 mmol) was added. The reaction was then warmed to rt and stirred for 1 hour, after which time complete conversion to product was observed by LCMS. TLC after 1 hour still showed the presence of some starting material and the reaction was continued stirring for an additional hour. After this time there was no change in TLC and the reaction was worked up. The reaction was quenched by slow addition of saturated ammonium chloride and the volatile solvent evaporated. The mixture was then diluted with EtOAc and water. The organic layer was then washed with brine, dried with sodium sulfate, and concentrated. The crude residue was purified by flash chromatography with a gradient of 8-66% EtOAc in Heptane to give the desired product as a yellow liquid (1.93 g, 50%). MS (ES+): m/z=183.1 (100) [MH+]. HPLC: tR=0.91 minute over 3 minutes. Purity: 76% [HPLC (LC/MS) at 220 nm].

Workup

  1. customThe resulting reaction
  2. temperatureafter which time the reaction was cooled back to −10° C.
  3. temperatureThe reaction was then warmed to rt
  4. stirringstirred for 1 hour
  5. waitTLC after 1 hour still showed
  6. stirringthe presence of some starting material and the reaction was continued stirring for an additional hour
  7. customThe reaction was quenched by slow addition of saturated ammonium chloride
  8. customthe volatile solvent evaporated
  9. additionThe mixture was then diluted with EtOAc and water
  10. washThe organic layer was then washed with brine
  11. dry with materialdried with sodium sulfate
  12. concentrationconcentrated
  13. customThe crude residue was purified by flash chromatography with a gradient of 8-66% EtOAc in Heptane

Sources & evidence

ORD record
ord-d24bab36b66b445ca3e07e92578d7d5a
Source dataset
uspto-grants-2014_04
Patent number
US08685993B2

Reaction notes

Loading…