Iodine → Tert-butyl 5-chloro-2,4-difluoro-6-iodonicotinate

HRID 1481777Notes

Reaction equation

HRID 1481777 reaction equation
[Li+].[Cl-].[Cl: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].[I:19]I>C1COCC1>[Cl:3][C:4]1[C:5]([I: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 807IodineHCID 433294Lithium ChlorideHCID 71281897Tert-butyl 5-chloro-2,4-difluoronicotinate

Product 1

HCID 89421790Tert-butyl 5-chloro-2,4-difluoro-6-iodonicotinateYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Into a solution of TMPMgCl LiCl (1.0 M×2.4 mL, 2.4 mmol) in THF at −45° C. was added dropwise a solution of tert-butyl 5-chloro-2,4-difluoronicotinate (0.4 g, 1.6 mmol) in THF (3.0 mL). The mixture was stirred for 20 min then iodine (0.61 g, 2.4 mmol) was added. After 15 min at −45° C., the temperature was allowed to warm to 0° C. 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 (0-5% ethyl acetate in hexanes) to give tert-butyl 5-chloro-2,4-difluoro-6-iodonicotinate (0.4 g, 67%).

Workup

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

Sources & evidence

ORD record
ord-e72e5152d7ec4c9fb8e8b0eca50611b4
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

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