1,1-Dibromo-1,2,2,2-tetrafluoroethane → Tert-butyl 5,6-dibromo-2,4-difluoronicotinate

HRID 1481771Notes

Reaction equation

HRID 1481771 reaction equation
[Li+].[Cl-].[Br:3][C:4]1[CH:5]=[N:6][C:7]([F:18])=[C:8]([C:16]=1[F:17])[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].[Br:19]C(Br)(F)C(F)(F)F>C1COCC1>[Br:3][C:4]1[C:5]([Br:19])=[N:6][C:7]([F:18])=[C:8]([C:16]=1[F:17])[C:9]([O:11][C:12]([CH3:14])([CH3:15])[CH3:13])=[O:10]

Participants

5

Reactant 3

HCID 1686881,1-Dibromo-1,2,2,2-tetrafluoroethaneHCID 433294Lithium ChlorideHCID 71281815Tert-butyl 5-bromo-2,4-difluoronicotinate

Product 1

HCID 89421760Tert-butyl 5,6-dibromo-2,4-difluoronicotinateYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Into a solution of TMPMgCl LiCl (1.0 M×6.8 mL, 6.8 mmol) in THF (5.0 mL) at −45° C. was added dropwise a solution of tert-butyl 5-bromo-2,4-difluoronicotinate (1.32 g, 4.5 mmol) in THF (5.0 mL). The mixture was stirred for 15 min then dibromotetrafluoroethane (1.0 mL, 6.8 mmol) was added. After 15 min at −45° C., the temperature was allowed to rise to room temperature. The reaction was quenched with saturated NH4Cl and extracted with ethyl acetate. The organic layers were combined, dried over sodium sulfate and evaporated. The residue was purified by silica chromatography (0-10% ethyl acetate in hexanes) to give tert-butyl 5,6-dibromo-2,4-difluoronicotinate (1.29 g, 77%).

Workup

  1. waitAfter 15 min at −45° C.
  2. customto rise to room temperature
  3. customThe reaction was quenched with saturated NH4Cl
  4. extractionextracted with ethyl acetate
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe residue was purified by silica chromatography (0-10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-b073b292df5e4ac4910db82692fd7ec1
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

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