N,N-Diethylaniline → Methyl 2-Chloro-5-iodonicotinate

HRID 704860Notes

Reaction equation

HRID 704860 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[CH2:5][NH:6][CH:7]=1.CCN(C1C=CC=CC=1)CC.P(Cl)(Cl)([Cl:25])=O>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C(#N)C.O>[Cl:25][C:5]1[C:4]([C:8]([O:10][CH3:11])=[O:9])=[CH:3][C:2]([I:1])=[CH:7][N:6]=1

Participants

7

Reactant 3

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 20073492Methyl 5-iodo-1,2-dihydro-3-pyridinecarboxylate

Product 1

HCID 2764559Methyl 2-Chloro-5-iodonicotinateYield 52%

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 66133Benzyl triethylammonium chlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

To a mixture containing 2.0 g of methyl 5-iodo-1,2-dihydro-3-pyridinecarboxylate, 1.6 g of diethylaniline, 1.64 g of benzyltriethylammonium chloride and 3.6 ml of distilled phosphorus oxychloride in 100 ml of dry acetonitrile are added 15 drops of water. The mixture is heated under reflux for 18 hours. After cooling the reaction mixture to room temperature, the solvent is removed under reduced pressure and the residue taken up in methylene chloride and extracted with water. The organic solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is chromatographed on a column of flash silica gel using methylene chloride as the eluent. Evaporation of the eluent yields a pale yellowish solid which is recrystallized from aqueous ethanol to give 1.1 g (52%) of methyl 2-chloro-5-iodo-3-pyridinecarboxylate as a white solid: m.p. 73°-73.5° C.; NMR (80 MHz, CDCl3) delta 3.96 (s, 3H), 8.43 (d, 1H, J=2.3 Hz), 8.71 (d, 1H, J=2.3 Hz).

Workup

  1. temperatureThe mixture is heated
  2. temperatureunder reflux for 18 hours
  3. customthe solvent is removed under reduced pressure
  4. extractionextracted with water
  5. dry with materialThe organic solution is dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is chromatographed on a column of flash silica gel
  8. customEvaporation of the eluent
  9. customyields a pale yellowish solid which
  10. customis recrystallized from aqueous ethanol

Sources & evidence

ORD record
ord-1cb63f5b05a44576ae5647d94207642d
Source dataset
uspto-grants-1991_01
Patent number
US04988813

Reaction notes

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