Ethanol → Ethyl 6-chloronicotinate

HRID 1655591Notes

Reaction equation

HRID 1655591 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.[CH2:11](O)[CH3:12].CN(C1C=CC=CN=1)C.Cl.CN(C)CCCN=C=NCC>O1CCCC1>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH2:11][CH3:12])=[O:7])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 218852-DimethylaminopyridineHCID 792226-Chloronicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 2799611Ethyl 6-chloronicotinate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 6.85 g (44 mmol) of 6-chloronicotinic acid dissolved in 50 mL of tetrahydrofuran was added ethanol (6 mL), dimethylaminopyridine (700 mg) and 1-(3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride (EDCl) (9.4 g, 49 mmol). The reaction was stirred at ambient temperature for 4 hours and then concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with water (2×), saturated sodium bicarbonate (2×) and brine, dried over sodium sulfate and concentrated in vacuo. The residue obtained was flash chromatographed on silica gel eluting with 10% ethyl acetate in hexane to afford 6.00 g of the title compound as a colorless oil. 1H NMR (CDCl3, 300 MHz) δ 1.40 (t, 3H), 4.40 (q, 2H), 7.40 (d, 1H), 8.25 (dd, 1H), 9.00 (d, 1H). MS (DCl/NH3) m/e 186/188 (M+H)+, 203/205 (M+H+NH3 )+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue was diluted with ethyl acetate
  3. washwashed with water (2×), saturated sodium bicarbonate (2×) and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue obtained
  7. customchromatographed on silica gel eluting with 10% ethyl acetate in hexane

Sources & evidence

ORD record
ord-58cd9eb0dd2d4303a7eef377311bf315
Source dataset
uspto-grants-1993_10
Patent number
US05250548

Reaction notes

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