Potassium Carbonate → HCID 57526945, compound

HRID 1452663Notes

Reaction equation

HRID 1452663 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:48])=[CH:32][C:33]([F:47])=[C:34]([NH:36][C:37](=[O:46])[O:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:35]=1>CN(C=O)C>[CH2:39]([O:38][C:37]([NH:36][C:34]1[C:33]([F:47])=[CH:32][C:31]([F:48])=[C:30]([C:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:13][CH:14]=2)[CH:35]=1)=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=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 57526944HCID 57526944, compound

Product 1

HCID 57526945HCID 57526945, compoundYield 24.5%

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 (4.58 g, 14.8 mmol), K2CO3 (6.14 g, 44.4 mmol) and PdCl2dppf (1.48 mmol, 1.21 g) was added a solution of benzyl 5-bromo-2,4-difluorophenylcarbamate (5.05, 14.8 mmol) in DMF (150 mL) at room temperature under argon. The mixture was heated to 80° C. under argon overnight. After cooling to room temperature, the mixture was filtered through Celite and the Celite was washed with EtOAc (3×100 mL). The filtrates were washed with H2O (3×200 mL), brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified flash chromatography (EtOAc/hexanes 1:9) to afford tert-butyl 4-(5-{[(benzyloxy)carbonyl]amino}-2,4-difluorophenyl)-3,6-dihydro-1(2H)-pyridinecarboxylate (1.60 g, 24.5%): 1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.45-7.35 (m, 5H), 6.85-6.70 (m, 1H), 5.95-5.85 (m, 1H), 5.20 (s, 2H), 4.05 (m, 2H), 3.6-3.5 (m, 2H), 2.5-2.4 (m, 2H), 1.50 (s, 9H); ESMS m/e: 443.3 (M−H+).

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered through Celite
  3. washthe Celite was washed with EtOAc (3×100 mL)
  4. washThe filtrates were washed with H2O (3×200 mL), brine (100 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified flash chromatography (EtOAc/hexanes 1:9)

Sources & evidence

ORD record
ord-ec127c0b17d04f068dae01e038248b68
Source dataset
uspto-grants-2009_01
Patent number
US07473698B2

Reaction notes

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