Phosphorus oxychloride → 4-Chloro-2-{[(3,5-dichloropyridin-4-yl)methyl]sulfanyl}-6-methylpyrimidine

HRID 630157Notes

Reaction equation

HRID 630157 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:18])[C:7]=1[CH2:8][S:9][C:10]1[N:15]=[C:14](O)[CH:13]=[C:12]([CH3:17])[N:11]=1.P(Cl)(Cl)([Cl:21])=O>>[Cl:21][C:14]1[CH:13]=[C:12]([CH3:17])[N:11]=[C:10]([S:9][CH2:8][C:7]2[C:2]([Cl:1])=[CH:3][N:4]=[CH:5][C:6]=2[Cl:18])[N:15]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178429460HCID 178429460, compound

Product 1

HCID 595894844-Chloro-2-{[(3,5-dichloropyridin-4-yl)methyl]sulfanyl}-6-methylpyrimidineYield 47.1%

Conditions

Temperature
75 °C

Procedure

A mixture of 2-{[(3,5-dichloropyridin-4-yl)methyl]sulfanyl}-6-methylpyrimidin-4-ol (2.0 g, 6.62 mmol) and phosphoryl trichloride (20 mL) was heated at 75° C. for 1 hour. The solvent was evaporated, and the crude residue was extracted into ethyl acetate (2×100 mL). The organic layer was washed with 10% sodium bicarbonate solution and brine. The organic layer was separated, dried over anhydrous sodium sulfate, and filtered. The solvent was evaporated, and the residue was purified by CombiFlash using 0-5% methanol in dichloromethane to provide 4-chloro-2-{[(3,5-dichloropyridin-4-yl)methyl]sulfanyl}-6-methylpyrimidine as a white solid (1.01 g, 47.1% yield); 1H NMR (400 MHz, DMSO-d6): δ 2.45 (s, 3H), 4.70 s, 2H), 7.40 (s, 1H), 8.66 (d, 211); M+1 321.2.

Workup

  1. customThe solvent was evaporated
  2. extractionthe crude residue was extracted into ethyl acetate (2×100 mL)
  3. washThe organic layer was washed with 10% sodium bicarbonate solution and brine
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customThe solvent was evaporated
  8. customthe residue was purified by CombiFlash

Sources & evidence

ORD record
ord-eb9908658a0343b69828750160b995b9
Source dataset
uspto-grants-2016_04
Patent number
US09315521B2

Reaction notes

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