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

HRID 2208100Notes

Reaction equation

HRID 2208100 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[CH2:11][C:10]([C:20]([C:26]([F:29])([F:28])[F:27])([C:22]([F:25])([F:24])[F:23])[OH:21])=[N:9]2)=[CH:4][CH:3]=1.C([CH:34]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH2:37][CH2:36][N:35]1[C:49]([OH:51])=[O:50])(C)(C)C.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[CH:12]1[N:8]([C:5]2[CH:4]=[CH:3][C:2]([C:38]3[CH2:37][CH2:36][N:35]([C:49]([O:51][C:13]([CH3:18])([CH3:14])[CH3:12])=[O:50])[CH2:34][CH:39]=3)=[CH:7][CH:6]=2)[N:9]=[C:10]([C:20]([C:26]([F:28])([F:27])[F:29])([C:22]([F:23])([F:24])[F:25])[OH:21])[CH2:11]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 67167277tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridin-1(2H)-carboxylic acidHCID 1184316661-(4-Bromo-phenyl)-5-(2-chloro-phenyl)-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole

Product 1

HCID 1184316715-(2-chloro-phenyl)-1-[4-(1-BOC-1,2,3,6-tetrahydropyridin-4-yl)-phenyl]-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazoleYield 144%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
85 °C

Procedure

1-(4-Bromo-phenyl)-5-(2-chloro-phenyl)-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole (500.0 mg, 1.00 mmol) prepared in Step 5 of Preparation 24, tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridin-1(2H)-carboxylic acid (370.0 mg, 1.20 mmol), potassium carbonate (690.0 mg, 4.98 mmol), and Pd(dppf)Cl2 (73.0 mg, 0.10 mmol) were added to a mixed solvent of 1,4-dioxane (15.0 mL) and distilled water (4.0 mL). The reaction mixture was stirred at 85° C. for 16 hours. Distilled water was added to the reaction mixture, which was then extracted with ethyl acetate. The extract was washed with distilled water and 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=1/5) to give 435.0 mg of the titled compound as a yellow liquid.

Workup

  1. distillationdistilled water (4.0 mL)
  2. additionDistilled water was added to the reaction mixture, which
  3. extractionwas then extracted with ethyl acetate
  4. washThe extract was washed with distilled water and brine
  5. dry with materialdried on anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give a yellow liquid residue
  8. customThe resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/5)

Sources & evidence

ORD record
ord-92b4407ed1bd4c7c90631684a2675e87
Source dataset
uspto-grants-2016_06
Patent number
US09376420B2

Reaction notes

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