Potassium Carbonate → 1-(2-chloro-phenyl)-5-[4-(1-BOC-1,2,3,6-tetrahydropyridin-4-yl)-phenyl]-3-pentafluoroethyl-4,5-dihydro-1H-pyrazole

HRID 2207957Notes

Reaction equation

HRID 2207957 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[N:11]=[C:10]([C:20]([F:26])([F:25])[C:21]([F:24])([F:23])[F:22])[CH2:9]2)=[CH:4][CH:3]=1.[C:27]([O:31][C:32]([N:34]1[CH2:39][CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28].C(=O)([O-])[O-].[K+].[K+]>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.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[Cl:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[N:12]1[CH:8]([C:5]2[CH:6]=[CH:7][C:2]([C:37]3[CH2:38][CH2:39][N:34]([C:32]([O:31][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:33])[CH2:35][CH:36]=3)=[CH:3][CH:4]=2)[CH2:9][C:10]([C:20]([F:26])([F:25])[C:21]([F:24])([F:22])[F:23])=[N:11]1

Participants

6

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 1184316755-(4-bromo-phenyl)-1-(2-chloro-phenyl)-3-pentafluoroethyl-4,5-dihydro-1H-pyrazole

Product 1

HCID 1184320161-(2-chloro-phenyl)-5-[4-(1-BOC-1,2,3,6-tetrahydropyridin-4-yl)-phenyl]-3-pentafluoroethyl-4,5-dihydro-1H-pyrazole

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

5-(4-Bromo-phenyl)-1-(2-chloro-phenyl)-3-pentafluoroethyl-4,5-dihydro-1H-pyrazole prepared in Step 3 of Preparation 1 (760.0 mg, 1.68 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridin-1-carboxylic acid tert-butyl ester (622.0 mg, 2.01 mmol), potassium carbonate (695.0 mg, 5.03 mmol), and Pd(dppf)Cl2 (137.0 mg, 0.17 mmol) were added to a mixed solvent of 1,4-dioxane (24.0 mL) and distilled water (6.0 mL). The reaction mixture was stirred for 15 minutes, additionally at 90° C. for 16 hours, and cooled to room temperature. Distilled water was added to the reaction mixture, which was then extracted with ethyl acetate. The extract was washed with brine, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure to give a yellow liquid residue. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/9) to give 630.0 mg of the titled compound as a white solid.

Workup

  1. distillationdistilled water (6.0 mL)
  2. temperaturecooled to room temperature
  3. additionDistilled water was added to the reaction mixture, which
  4. extractionwas then extracted with ethyl acetate
  5. washThe extract was washed with brine
  6. dry with materialdried on anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto give a yellow liquid residue
  9. customThe resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/9)

Sources & evidence

ORD record
ord-6a51144c7ac842a186ea521131d9a38b
Source dataset
uspto-grants-2016_06
Patent number
US09376420B2

Reaction notes

Loading…