Potassium Carbonate → tert-butyl 4-[2,4-difluoro-5-(isobutyrylamino)phenyl]-3,6-dihydro-1(2H)-pyridinecarboxylate

HRID 1269175Notes

Reaction equation

HRID 1269175 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH:14]=2)O1.C([O-])([O-])=O.[K+].[K+].Br[C:30]1[C:31]([F:43])=[CH:32][C:33]([F:42])=[C:34]([NH:36][C:37](=[O:41])[CH:38]([CH3:40])[CH3:39])[CH:35]=1>CN(C=O)C>[F:43][C:31]1[CH:32]=[C:33]([F:42])[C:34]([NH:36][C:37](=[O:41])[CH:38]([CH3:39])[CH3:40])=[CH:35][C:30]=1[C:9]1[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:13][CH:14]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 16757161N-(5-bromo-2,4-difluorophenyl)-2-methylpropanamide

Product 1

HCID 16756286tert-butyl 4-[2,4-difluoro-5-(isobutyrylamino)phenyl]-3,6-dihydro-1(2H)-pyridinecarboxylateYield 59%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a 250-mL RB flask containing tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate (3.31 g, 10.7 mmol), K2CO3 (4.44 g, 32.1 mmol) and PdCl2dppf (870 mg, 1.07 mmol) was added a solution of N-(5-bromo-2,4-difluorophenyl)-2-methylpropanamide (3.28 g, 11.8 mmol) in DMF (100 mL) at room temperature under argon. The mixture was heated to 80° C. under argon overnight, cooled to room temperature, filtered through celite and the celite was washed with EtOAc (3×20 mL). The filtrates were washed with H2O (20 mL), brine (20 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (10%–20% EtOAc/hexane) to give 2.4 g (6.31 mmol, 59%) of tert-butyl 4-[2,4-difluoro-5-(isobutyrylamino)phenyl]-3,6-dihydro-1(2H)-pyridine carboxylate: ESMS m/e: 379.3 (M−H)+.

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered through celite
  3. washthe celite was washed with EtOAc (3×20 mL)
  4. washThe filtrates were washed with H2O (20 mL), brine (20 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (10%–20% EtOAc/hexane)

Sources & evidence

ORD record
ord-16f613aeaf754373a8ed5c91ef5bbfd7
Source dataset
uspto-grants-2007_04
Patent number
US07199135B2

Reaction notes

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