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

HRID 2208047Notes

Reaction equation

HRID 2208047 reaction equation
Br[C:2]1[CH:3]=[C:4]([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]([C:26]([F:29])([F:28])[F:27])([C:22]([F:25])([F:24])[F:23])[OH:21])[CH2:9]2)[CH:5]=[CH:6][CH:7]=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[N:12]1[CH:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([C:38]3[CH2:37][CH2:36][N:35]([C:49]([O:51][C:4]([CH3:8])([CH3:5])[CH3:3])=[O:50])[CH2:34][CH:39]=3)[CH:3]=2)[CH2:9][C:10]([C:20]([C:22]([F:23])([F:24])[F:25])([C:26]([F:29])([F:27])[F:28])[OH:21])=[N: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 1184321755-(3-Bromo-phenyl)-1-(2-chloro-phenyl)-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole

Product 1

HCID 1184317301-(2-chloro-phenyl)-5-[3-(1-BOC-1,2,3,6-tetrahydropyridin-4-yl)-phenyl]-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazoleYield 123.4%

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-(3-Bromo-phenyl)-1-(2-chloro-phenyl)-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole (1.1 g, 2.2 mmol) prepared in Step 4 of Preparation 16, tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridin-1 (2H)-carboxylic acid (805.5 mg, 2.6 mmol), potassium carbonate (900.0 mg, 6.5 mmol), and Pd(dppf)Cl2 (159.0 mg, 0.20 mmol) were added to a mixed solvent of 1,4-dioxane (35.0 mL) and distilled water (9.0 mL). The reaction mixture was stirred for 15 minutes, additionally at 90° C. for 16 hours, and then ethyl acetate was added thereto. The reaction mixture 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=1/4) to give 820.0 mg of the titled compound as a white solid.

Workup

  1. distillationdistilled water (9.0 mL)
  2. additionethyl acetate was added
  3. washThe reaction mixture was washed with distilled water and brine
  4. dry with materialdried on anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto give a yellow liquid residue
  7. customThe resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/4)

Sources & evidence

ORD record
ord-0dc3dd3859aa49e0b712a29e494be8a0
Source dataset
uspto-grants-2016_06
Patent number
US09376420B2

Reaction notes

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