Acetic Acid → Ethyl 3-(3,5-dibromopyridin-4-yl)propanoate

HRID 2277661Notes

Reaction equation

HRID 2277661 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:9])[C:7]=1[CH3:8].[Li+].CC([N-]C(C)C)C.[CH2:18]([O:20][C:21](=[O:24])[CH2:22]Br)[CH3:19].CC(O)=O>C1COCC1>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:9])[C:7]=1[CH2:8][CH2:22][C:21]([O:20][CH2:18][CH3:19])=[O:24]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7748Ethyl bromoacetateHCID 8193383,5-Dibromo-4-methylpyridineHCID 2724682Lithium diisopropylamide

Product 1

HCID 86685955Ethyl 3-(3,5-dibromopyridin-4-yl)propanoateYield 33.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3,5-dibromo-4-methylpyridine (20 g, 0.08 mol) in THF (50 mL) was added over a period of 1 hour to a solution of LDA (0.088 mol) [generated from N,N-diisopropylamine (8.9 g, 0.088 mol) and n-butyllithium (35 mL, 0.088 mol, 2.5 M in hexane) in 400 mL THF] at −78° C. The resulting dark red solution was stirred at −78° C. for 30 min before ethylbromoacetate (33.4 g, 0.2 mol) in THF (50 mL) was added over a period of 30 min. The reaction mixture was stirred for an additional 2.5 hour at −78° C. before 10% AcOH was added (resulting in a pH=4-5). The reaction mixture was then allowed to warm up to room temperature. After evaporation of the solvents, the residue was poured into satd. aq. NaHCO3 solution and extracted with EtOAc (100 mL×3). The combined organic layers were dried over anhy. Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography to afford the title compound (9 g, 33.5%) as a yellow solid. MS: 337.7 (M+H+, 2Br).

Workup

  1. additionwas added over a period of 30 min
  2. additionwas added (
  3. customresulting in a pH=4-5)
  4. customAfter evaporation of the solvents
  5. additionthe residue was poured into satd
  6. extractionaq. NaHCO3 solution and extracted with EtOAc (100 mL×3)
  7. customThe combined organic layers were dried over anhy
  8. filtrationNa2SO4, filtered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-fd398c3fb10d420fbb5cf4a9faaf31a3
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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