Phosphorus oxychloride → HCID 118232987, compound

HRID 1749212Notes

Reaction equation

HRID 1749212 reaction equation
[CH3:1][CH:2]1[CH2:6][N:5]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[NH:4][C:3]1=O.P(Cl)(Cl)([Cl:16])=O>C(#N)C>[Cl:16][C:3]1[CH:2]([CH3:1])[CH2:6][N:5]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[N:4]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 118232985HCID 118232985, compound

Product 1

HCID 118232987HCID 118232987, compoundYield 76.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

Crude 4-methyl-1-(pyridin-3-yl)pyrazolidin-3-one (35.2 g, ˜82.4 mmol) was introduced into a 250 mL three-neck round bottom flask equipped with a reflux condenser. Acetonitrile (100 mL) was then added. To this yellow mixture was added phosphoryl chloride (11.56 mL, 124 mmol) slowly. The yellow slurry was stirred at 75° C. for 1 hour. The mixture was cooled down and concentrated to remove volatiles. The brown residue was carefully quenched with water (120 mL), and basified with NaOH (50 wt % in water) to pH 10 while keeping the temperature below 60° C. The mixture was then extracted with ethyl acetate (3×150 mL). The combined organic extracts were washed with water (80 mL) and concentrated under reduced pressure to afford the crude product as dark purple oil. The crude product was purified by flash column chromatography using 0-70% ethyl acetate/hexanes as eluent to provide the title compound as a brown oil (12.3 g, 76% over two steps): 1H NMR (400 MHz, CDCl3) δ 8.27 (dd, J=2.8, 0.7 Hz, 1H), 8.15 (dd, J=4.6, 1.4 Hz, 1H), 7.38 (ddd, J=8.4, 2.9, 1.4 Hz, 1H), 7.18 (ddd, J=8.4, 4.7, 0.7 Hz, 1H), 4.17-4.06 (m, 1H), 3.47 (t, J=8.9 Hz, 1H), 3.44-3.34 (m, 1H), 1.37 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 148.17, 142.07, 141.10, 134.74, 123.39, 119.92, 56.62, 43.62, 16.16; EIMS m/z 195 ([M]+).

Workup

  1. customequipped with a reflux condenser
  2. temperatureThe mixture was cooled down
  3. concentrationconcentrated
  4. customto remove volatiles
  5. customThe brown residue was carefully quenched with water (120 mL)
  6. customthe temperature below 60° C
  7. extractionThe mixture was then extracted with ethyl acetate (3×150 mL)
  8. washThe combined organic extracts were washed with water (80 mL)
  9. concentrationconcentrated under reduced pressure
  10. customto afford the crude product as dark purple oil
  11. customThe crude product was purified by flash column chromatography

Sources & evidence

ORD record
ord-8572f2f99e42418098dfb49668f12833
Source dataset
uspto-grants-2015_10
Patent number
US09156813B1

Reaction notes

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