Ethanol → Ethyl 2,6-dichloro-5-fluoropyridine-3-carboxylate

HRID 1655596Notes

Reaction equation

HRID 1655596 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[CH:6][C:5]([F:11])=[C:4]([Cl:12])[N:3]=1.S(Cl)(Cl)=O.[CH2:17](N(CC)CC)[CH3:18].C(O)C.C(=O)(O)[O-].[Na+]>CCOCC>[Cl:1][C:2]1[C:7]([C:8]([O:10][CH2:17][CH3:18])=[O:9])=[CH:6][C:5]([F:11])=[C:4]([Cl:12])[N:3]=1

Participants

7

Reactant 5

HCID 702EthanolHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 27336592,6-Dichloro-5-fluoronicotinic acid

Product 1

HCID 13210747Ethyl 2,6-dichloro-5-fluoropyridine-3-carboxylateYield 94%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

2,6-Dichloro-5-fluoropyridine-3-carboxylic acid (5.00 g, 23.81 mmol) was mixed with ~13 mL of thionyl chloride under nitrogen. The reaction was heated and the excess thionyl chloride was distilled off. The resulting liquid was diluted with ~5 mL methylene chloride, cooled to 0° C. and treated with 4.98 mL (1.5 equivalents) of triethylamine followed by 2.79 mL (2.0 equivalents) of ethanol dropwise. The reaction was allowed to warm to ambient temperature and stirred for 1 hour. A 1:1 mixture of sodium bicarbonate solution and ether (~80 mL) was added and the organic layer was washed with saturated sodium bicarbonate solution, 1N phosphoric acid and brine, dried over magnesium sulfate and concentrated in vacuo. The residue obtained was flash chromatographed on silica gel eluting with 5% ethyl acetate in hexane to give the title compound (5.32 g, 94%) as a yellow liquid. 1H NMR (CDCl3, 300 MHz) δ 1.42 (t, 3 H), 4.43 (q, 2H), 8.00 (d, 1H). MS (DCl/NH3) m/e 239 (M+H)+.

Workup

  1. temperatureThe reaction was heated
  2. distillationthe excess thionyl chloride was distilled off
  3. additionThe resulting liquid was diluted with ~5 mL methylene chloride
  4. temperatureto warm to ambient temperature
  5. additionwas added
  6. washthe organic layer was washed with saturated sodium bicarbonate solution, 1N phosphoric acid and brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue obtained
  10. customchromatographed on silica gel eluting with 5% ethyl acetate in hexane

Sources & evidence

ORD record
ord-b579dfeb1563413dae88bf41da3a7925
Source dataset
uspto-grants-1993_10
Patent number
US05250548

Reaction notes

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