N,N-Diethylaniline → 2,5-Dichloro-4,6-dimethylpyrimidine

HRID 1524920Notes

Reaction equation

HRID 1524920 reaction equation
[Cl:1][C:2]1[C:3]([CH3:10])=[N:4][C:5](O)=[N:6][C:7]=1[CH3:8].O=P(Cl)(Cl)[Cl:13].N(C1C=CC=CC=1)(CC)CC>>[Cl:13][C:5]1[N:4]=[C:3]([CH3:10])[C:2]([Cl:1])=[C:7]([CH3:8])[N:6]=1

Participants

4

Reactant 3

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 178433498HCID 178433498, compound

Product 1

HCID 138809112,5-Dichloro-4,6-dimethylpyrimidineYield 83%

Conditions

Temperature
125 °C

Procedure

To 5-chloro-4,6-dimethylpyrimidin-2-ol (992 mg, 6.26 mmol) was added POCl3 (2.22 mL, 23.77 mmol) followed by Et2NPh (0.75 mL, 4.69 mmol) dropwise. The mixture was heated at 125° C. for 2 h. At approximately 2 h the reaction became homogeneous and was checked by HPLC and it showed all starting material had been consumed. The mixture was allowed to cool to room temperature and was then added dropwise to ice. After the ice had melted there was a white solid in a pink liquid. The aqueous layer was extracted with DCM and the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Chromatography (Hex to 10% EtOAc/Hex) afforded the desired product as a white solid (915 mg, 83%). 1H NMR (500 MHz, CDCl3): 2.57 (s, 6H).

Workup

  1. customhad been consumed
  2. temperatureto cool to room temperature
  3. additionwas then added dropwise to ice
  4. extractionThe aqueous layer was extracted with DCM
  5. dry with materialthe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d9cb65f05665445bb96266f4badb18c7
Source dataset
uspto-grants-2015_07
Patent number
US09079911B2

Reaction notes

Loading…