Phosphorus pentachloride → methyl 6-chloro-5-cyano-2-methylnicotinate

HRID 1397349Notes

Reaction equation

HRID 1397349 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8]([C:10]#[N:11])[C:7](O)=[N:6][C:5]=1[CH3:13].P(Cl)(Cl)(Cl)(Cl)[Cl:16]>O=P(Cl)(Cl)Cl>[Cl:16][C:7]1[C:8]([C:10]#[N:11])=[CH:9][C:4]([C:3]([O:2][CH3:1])=[O:14])=[C:5]([CH3:13])[N:6]=1

Participants

4

Reactant 2

HCID 24819Phosphorus pentachlorideHCID 178498192HCID 178498192, compound

Product 1

HCID 1471652methyl 6-chloro-5-cyano-2-methylnicotinateYield 137%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of methyl-5-cyano-6-hydroxy-2-methylnicotinate (2.0 g, 10.41 mmol), POCl3 (40 mL) and PCl5 (1.08 g, 5.2 mmol) was heated to 110° C. for 24 h. The reaction mixture was concentrated under reduced pressure and quenched with ice-water. The organic product was extracted with EtOAc and the organic layer was washed with H2O and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 10-15% EtOAc in petroleum ether) to afford methyl 6-chloro-5-cyano-2-methylnicotinate (1.5 g, yield 68%). 1H NMR (300 MHz, CDCl3) δ 8.48 (s, 1H), 3.96 (s, 3H), 2.90 (s, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customquenched with ice-water
  3. extractionThe organic product was extracted with EtOAc
  4. washthe organic layer was washed with H2O and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 10-15% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-8f459add52d948f1a33c8c74ee5bd6a6
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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