Potassium Carbonate → (R)-2-(5-bromopyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamide

HRID 510179Notes

Reaction equation

HRID 510179 reaction equation
Cl.[NH2:2][C@H:3]([CH:12]([CH3:14])[CH3:13])[C:4]([NH:6][CH2:7][C:8]([F:11])([F:10])[F:9])=[O:5].[Br:15][C:16]1[CH:17]=[N:18][CH:19]=[C:20](Br)[CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.C(OCC)(=O)C.[Cu]I>[Br:15][C:16]1[CH:21]=[C:20]([NH:2][C@H:3]([CH:12]([CH3:14])[CH3:13])[C:4]([NH:6][CH2:7][C:8]([F:9])([F:10])[F:11])=[O:5])[CH:19]=[N:18][CH:17]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 693693,5-DibromopyridineHCID 117628603(R)-2-amino-3-methyl-N-(2,2,2-trifluoroethyl)butanamide hydrochloride

Product 1

HCID 89495326(R)-2-(5-bromopyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamideYield 46.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

In a round bottomed flask equipped with a magnetic stirrer, (R)-2-amino-3-methyl-N-(2,2,2-trifluoroethyl)butanamide hydrochloride (1-3b) (20 g, 85 mmol), 3,5-Dibromopyridine (30.3 g, 128 mmol), Potassium carbonate (35.3 g, 256 mmol) were suspended in DMSO (71 ml, 1.2M) and reaction mixture was purged with nitrogen for 20 minutes, then Copper(I) Iodide (0.974 g, 5.1 mmol) was added and the reaction mixture was slowly heated to 120° C. overnight. The cooled reaction mixture was then partitioned between Isopropanol (IPA):Chloroform (1:3) and Water, the aqueous layer was extracted with three times with IPA:Chloroform mixture. The combined organic layers were extracted with 1M solution of EDTA disodium salt, dried over anhydrous magnesium sulfate, filtered and concentrated to give the crude sample. Purification on a silica gel column using a gradient 0-40% ethyl acetate:hexane gave an orange solid which was taken up in ethyl acetate and concentrated to an oil, hexane was added dropwise while stirring, a white solid crystallized which was filtered, washed with hexane and dried under vacuum to give 14 g, (46.4%) the title compound, I-3, as a white solid.

Workup

  1. customIn a round bottomed flask equipped with a magnetic stirrer
  2. customreaction mixture
  3. customwas purged with nitrogen for 20 minutes
  4. customThe cooled reaction mixture
  5. customwas then partitioned between Isopropanol (IPA)
  6. extractionChloroform (1:3) and Water, the aqueous layer was extracted with three times with IPA
  7. extractionThe combined organic layers were extracted with 1M solution of EDTA disodium salt
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the crude sample
  12. customPurification on a silica gel column
  13. customhexane gave an orange solid which
  14. concentrationconcentrated to an oil, hexane
  15. additionwas added dropwise
  16. customa white solid crystallized which
  17. filtrationwas filtered
  18. washwashed with hexane
  19. customdried under vacuum

Sources & evidence

ORD record
ord-52c25ea0d8064d0bae63f8de594bf526
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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