Heptane → Tert-butyl 5-bromo-2,4-difluoronicotinate

HRID 1481770Notes

Reaction equation

HRID 1481770 reaction equation
[F:1][C:2]1[N:14]=[CH:13][CH:12]=[C:11]([F:15])[C:3]=1[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].[Li+].CC([N-]C(C)C)C.CCCCCCC.[Br:31]C(Br)(Cl)C(Cl)(Cl)Cl>C1COCC1>[Br:31][C:12]1[CH:13]=[N:14][C:2]([F:1])=[C:3]([C:11]=1[F:15])[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5]

Participants

6

Reactant 4

HCID 8900HeptaneHCID 2724682Lithium diisopropylamideHCID 137826771,1-Dibromo-1,2,2,2-tetrachloroethaneHCID 71281946Tert-butyl 2,4-difluoronicotinate

Product 1

HCID 71281815Tert-butyl 5-bromo-2,4-difluoronicotinateYield 42.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Into a solution of tert-butyl 2,4-difluoronicotinate (0.95 g, 4.4 mmol) in THF (15 mL) at −78° C. was added a solution of LDA in heptane (1.5 M×3.5 mL, 5.3 mmol) dropwise. The mixture was stirred for 10 min. Then a solution of dibromotetrachloroethane (1.86 g, 5.7 mmol) in THF (4.0 mL) was added dropwise. After 15 min, the temperature was allowed to rise to room temperature slowly. The reaction was quenched with saturated NH4Cl. The mixture was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and evaporated to give a residue, which was purified by silica chromatography (5-50% dichloromethane in hexanes) to give tert-butyl 5-bromo-2,4-difluoronicotinate (0.55 g, 42%).

Workup

  1. waitAfter 15 min
  2. customto rise to room temperature
  3. customThe reaction was quenched with saturated NH4Cl
  4. extractionThe mixture was extracted with ethyl acetate
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. customevaporated
  7. customto give a residue, which
  8. customwas purified by silica chromatography (5-50% dichloromethane in hexanes)

Sources & evidence

ORD record
ord-40f1cead9577488ea2d7dca0e6ee552e
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

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