N,N-Diethylaniline → 2-Chloro-4,5,6-trimethylpyrimidine

HRID 1524912Notes

Reaction equation

HRID 1524912 reaction equation
[CH3:1][C:2]1[C:7]([CH3:8])=[C:6]([CH3:9])[N:5]=[C:4](O)[N:3]=1.O=P(Cl)(Cl)[Cl:13].N(C1C=CC=CC=1)(CC)CC>>[Cl:13][C:4]1[N:3]=[C:2]([CH3:1])[C:7]([CH3:8])=[C:6]([CH3:9])[N:5]=1

Participants

4

Reactant 3

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 178433497HCID 178433497, compound

Product 1

HCID 125019872-Chloro-4,5,6-trimethylpyrimidineYield 101.9%

Procedure

To 4,5,6-trimethylpyrimidin-2-ol (3.69 g, 26.7 mmol) was added POCl3 (21.7 mL, 26.7 mmol) followed by Et2NPh (2.17 mL, 13.6 mmol) dropwise. The mixture was heated at reflux for 48 h and then added to ice dropwise. The aqueous layer was extracted with EtOAc (2×). Extraction was difficult due to a large amount of precipitate. The aqueous layer pH was adjusted to pH 4-5 with 28% NH4OH and was filtered through Celite®. The aqueous layer was then extracted with DCM and the combined organic extracts dried over Na2SO4, filtered and concentrated in vacuo to a yellow solid. Chromatography (FCC) (0 to 30% EtOAc/Hex) afforded 2-chloro-4,5,6-trimethylpyrimidine (4.26 g, 100%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 48 h
  3. additionadded to ice dropwise
  4. extractionThe aqueous layer was extracted with EtOAc (2×)
  5. extractionExtraction
  6. filtrationwas filtered through Celite®
  7. extractionThe aqueous layer was then extracted with DCM
  8. dry with materialthe combined organic extracts dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo to a yellow solid

Sources & evidence

ORD record
ord-1e38fb8e4540443d89144b6b3def9992
Source dataset
uspto-grants-2015_07
Patent number
US09079911B2

Reaction notes

Loading…