Ammonia → 3-(2,5-Dimethyl-pyrrol-1-yl)-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid methyl ester

HRID 444941Notes

Reaction equation

HRID 444941 reaction equation
[F-].[K+].[CH3:3][O:4][C:5]([C:7]1[C:12]([N:13]2[C:17]([CH3:18])=[CH:16][CH:15]=[C:14]2[CH3:19])=[CH:11][C:10]([C:20]([F:23])([F:22])[F:21])=[C:9](Br)[N:8]=1)=[O:6].[Si]([C:29]([F:32])([F:31])[F:30])(C)(C)C.N>[Cu]I.CN(C=O)C>[CH3:3][O:4][C:5]([C:7]1[C:12]([N:13]2[C:17]([CH3:18])=[CH:16][CH:15]=[C:14]2[CH3:19])=[CH:11][C:10]([C:20]([F:23])([F:22])[F:21])=[C:9]([C:29]([F:32])([F:31])[F:30])[N:8]=1)=[O:6]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 522689Potassium FluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 584423696-Bromo-3-(2,5-dimethyl-pyrrol-1-yl)-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester2×

Product 1

HCID 866576693-(2,5-Dimethyl-pyrrol-1-yl)-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A stirred mixture of KF (2.12 g, 5.62 mmol) and CuI (0.490 g, 8.43 mmol) was heated in a sealed 10.0-20.0 ml microwave vial under vacuum until a slight greenish colour began to appear. The vial was then placed under nitrogen to cool. A solution 6-bromo-3-(2,5-dimethyl-pyrrol-1-yl)-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (Intermediate D) (2.64 ml, 16.86 mmol) in 1:1 dry DMF/dry NMP (14 ml) was then added, followed by TMS-CF3 (2.64 ml, 16.86 mmol). A new septum was then used to seal the vial and the reaction mixture was heated using microwave radiation with stirring at 100° C. for 3 h and allowed to cool. The mixture was added to 5M NH3 solution (50 ml) and then extracted with diethyl ether (4×50 ml). The combined organic extracts were washed with 5M NH3 solution (3×20 ml), 1M HCl (50 ml), sat. sodium bicarbonate solution (2×50 ml), brine (50 ml), dried (MgSO4) and concentrated in vacuo to give a brown oil. The crude material was purified by chromatography on silica eluting with Iso-hexane/EtOAc, 0-10% to afford the title compound as an orange solid; LC-MS Rt 1.37 min; MS m/z 367.1 [M+H]+; Method 2 minLC_v003.

Workup

  1. temperaturewas heated in a sealed 10.0-20.0 ml microwave vial under vacuum until a slight greenish colour
  2. temperatureto cool
  3. customto seal the vial and the reaction mixture
  4. temperaturewas heated
  5. temperatureto cool
  6. extractionextracted with diethyl ether (4×50 ml)
  7. washThe combined organic extracts were washed with 5M NH3 solution (3×20 ml), 1M HCl (50 ml), sat. sodium bicarbonate solution (2×50 ml), brine (50 ml)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customto give a brown oil
  11. customThe crude material was purified by chromatography on silica eluting with Iso-hexane/EtOAc, 0-10%

Sources & evidence

ORD record
ord-a2a9e63e0fa840c4afa38bf9d77cdda2
Source dataset
uspto-grants-2013_07
Patent number
US08476269B2

Reaction notes

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