Potassium Carbonate → Tert-butyl 3-(4,6-bistrifluoromethylpyridin-2-yl)propylcarbamate

HRID 444793

Reaction equation

HRID 444793 reaction equation
[CH2:1]([NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8])[CH:2]=[CH2:3].C12BC(CCC1)CCC2.Br[C:22]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[C:24]([C:32]([F:35])([F:34])[F:33])[N:23]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].O>[F:31][C:28]([F:29])([F:30])[C:26]1[CH:25]=[C:24]([C:32]([F:33])([F:34])[F:35])[N:23]=[C:22]([CH2:3][CH2:2][CH2:1][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8])[CH:27]=1

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 4067274tert-butyl N-(prop-2-en-1-yl)carbamateHCID 85875928Pyridine, 2-bromo-4,6-bis(trifluoromethyl)-

Product 1

HCID 86650694Tert-butyl 3-(4,6-bistrifluoromethylpyridin-2-yl)propylcarbamateYield 74%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of tert-butyl allylcarbamate (1.95 g, 12.4 mmol) in THF (12 mL), 0.5 mol/L 9-borabicyclo[3.3.1]nonane (29.8 mL, 14.9 mmol) was added under argon atmosphere at room temperature. After stirred at room temperature for 4 h, a solution of 2-bromo-4,6-bistrifluoromethylpyridine (3.65 g, 12.4 mmol) in DMF (12 mL), Pd(OAc)2 (278 mg, 1.24 mmol), DPPF (859 mg, 1.55 mmol) and K2CO3 (2.92 g, 21.1 mmol) were added to the reaction mixture and stirred at room temperature for 7 h. To the reaction mixture, water was added and the crude product was extracted with EtOAc, washed with brine, dried over NaSO4 and the solvent was removed in vacuo. The crude product was purified by column chromatography (Hexane:EtOAc 10:1→2:1) to yield tert-butyl 3-(4,6-bistrifluoromethylpyridin-2-yl)propylcarbamate (3.41 g, 74%) as a colorless solid. 1H NMR (CDCl3, 400 MHz) δ 1.44 (9H, s), 1.96-2.03 (2H, m), 2.98-3.02 (2H, m), 3.20-3.25 (2H, m), 4.71 (1H, brs), 7.59 (1H, s), 7.72 (1H, s). CIMS (+) 373 [M+H]+.

Workup

  1. stirringstirred at room temperature for 7 h
  2. extractionthe crude product was extracted with EtOAc
  3. washwashed with brine
  4. dry with materialdried over NaSO4
  5. customthe solvent was removed in vacuo
  6. customThe crude product was purified by column chromatography (Hexane:EtOAc 10:1→2:1)

Sources & evidence

ORD record
ord-a2417668deaa487fb23f75a774839b97
Source dataset
uspto-grants-2013_07
Patent number
US08476261B2

Linked notes

Loading…