Ethyl chloroformate → Ethyl 3,5-dibromoisonicotinate

HRID 630147Notes

Reaction equation

HRID 630147 reaction equation
[Li+].CC([N-]C(C)C)C.[Br:9][C:10]1[CH:11]=[N:12][CH:13]=[C:14]([Br:16])[CH:15]=1.Cl[C:18]([O:20][CH2:21][CH3:22])=[O:19]>C1COCC1>[Br:9][C:10]1[CH:11]=[N:12][CH:13]=[C:14]([Br:16])[C:15]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19]

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 693693,5-DibromopyridineHCID 2724682Lithium diisopropylamide

Product 1

HCID 46311332Ethyl 3,5-dibromoisonicotinateYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of LDA (2 M solution in THF/heptane/ethylbenzene) (2.26 g, 10.54 mL, 21.06 mmol) in anhydrous THF (20 mL) under nitrogen atmosphere cooled to −78° C. was added a solution of the 3,5-dibromopyridine (5.0 g, 21.10 mmol) in anhydrous THF (40 mL) at −78° C. The reaction mixture was allowed to stir at the same temperature for 45 minutes. Then, a solution of chloro(ethoxy)methanone (22.90 g, 211.02 mmol) was added slowly over 15 minutes. After stirring for 20 minutes, the reaction mixture was quenched with saturated aqueous NaHCO3. The mixture was extracted with ethyl acetate (3×100 mL), and the combined organic layer was washed with water and brine. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated, and the residue was purified through CombiFlash using 0-10% ethyl acetate in hexane to provide ethyl 3,5-dibromopyridine-4-carboxylate as pale yellow oil (5.98 g, 92% yield); 1H NMR (400 MHz, DMSO-d6): δ1.43 (t, 3H), 4.49 (q, 2H), 8.67 (s, 2H); M+307.9.

Workup

  1. stirringAfter stirring for 20 minutes
  2. customthe reaction mixture was quenched with saturated aqueous NaHCO3
  3. extractionThe mixture was extracted with ethyl acetate (3×100 mL)
  4. washthe combined organic layer was washed with water and brine
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customThe filtrate was evaporated
  8. customthe residue was purified through CombiFlash

Sources & evidence

ORD record
ord-5171fd7750e348eab84993d2281d73b4
Source dataset
uspto-grants-2016_04
Patent number
US09315521B2

Reaction notes

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