Hexachloroethane → Tert-butyl 5-chloro-2,4-difluoronicotinate

HRID 1481776Notes

Reaction equation

HRID 1481776 reaction equation
[Li+].CC([N-]C(C)C)C.[F:9][C:10]1[N:22]=[CH:21][CH:20]=[C:19]([F:23])[C:11]=1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[Cl:24]C(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1>[Cl:24][C:20]1[CH:21]=[N:22][C:10]([F:9])=[C:11]([C:19]=1[F:23])[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]

Participants

5

Reactant 3

HCID 6214HexachloroethaneHCID 2724682Lithium diisopropylamideHCID 71281946Tert-butyl 2,4-difluoronicotinate

Product 1

HCID 71281897Tert-butyl 5-chloro-2,4-difluoronicotinateYield 48.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Into a solution of LDA in THF (20 mL, 12 mmol) was added a solution of tert-butyl 2,4-difluoronicotinate (2.14 g, 10 mmol) in THF (12 mL) at −78° C. The mixture was stirred for 30 min and then a solution of hexachloroethane (2.96 g, 12.5 mmol) in THF (7.0 mL) was added. The temperature was allowed to rise to 0° C. The reaction was then quenched with saturated NH4Cl. The mixture was extracted with ethyl acetate and the organic layers were combined, dried over sodium sulfate, evaporated and purified by silica chromatography (0-8% ethyl acetate in hexanes) to give tert-butyl 5-chloro-2,4-difluoronicotinate (1.2 g, 48%).

Workup

  1. customto rise to 0° C
  2. customThe reaction was then quenched with saturated NH4Cl
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. custompurified by silica chromatography (0-8% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-88a20d163dd5466797e222ab737558cc
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

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