Potassium Carbonate → 1-(1-(4-chloro-3-methoxyphenyl)piperidin-4-yl)-2-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)ethanone

HRID 1804834Notes

Reaction equation

HRID 1804834 reaction equation
Cl[CH2:2][C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][CH3:19])[CH:12]=2)[CH2:7][CH2:6]1)=[O:4].[CH3:20][C:21]1[NH:25][N:24]=[C:23]([C:26]([F:29])([F:28])[F:27])[CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([N:8]2[CH2:9][CH2:10][CH:5]([C:3](=[O:4])[CH2:2][N:25]3[C:21]([CH3:20])=[CH:22][C:23]([C:26]([F:29])([F:28])[F:27])=[N:24]3)[CH2:6][CH2:7]2)=[CH:12][C:13]=1[O:18][CH3:19]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1390771H-Pyrazole, 3-methyl-5-(trifluoromethyl)-HCID 866397972-Chloro-1-(1-(4-chloro-3-methoxyphenyl)piperidin-4-yl)ethanone

Product 1

HCID 685547771-(1-(4-chloro-3-methoxyphenyl)piperidin-4-yl)-2-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)ethanoneYield 81.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 2-chloro-1-(1-(4-chloro-3-methoxyphenyl)piperidin-4-yl)ethanone (580 mg, 1.919 mmol; see Example 1a, Step 2), 5-methyl-3-(trifluoromethyl)-1H-pyrazole (576 mg, 3.84 mmol), potassium carbonate (796 mg, 5.76 mmol) and acetonitrile (20 mL) was stirred at RT for 12 h. After this time, the solvent was removed under reduced pressure and the resultant residue was partitioned between EtOAc (100 mL) and water (50 mL). The organic phase was washed with brine, dried (Na2SO4) and concentrated on a rotary evaporator to yield a residue. The residue was purified by flash chromatography using a 40 g silica gel cartridge and gradient elution from 10:1 Hex/EtOAc to 1:1 Hex/EtOAc. The fractions containing the product were pooled and concentrated on a rotary evaporator to give 1-(1-(4-chloro-3-methoxyphenyl)piperidin-4-yl)-2-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)ethanone (650 mg, 1.563 mmol, 81% yield) as clear oil. 1H-NMR (400 MHz, CDCl3) δ ppm 7.19 (1 H, d, J=8.57 Hz), 6.49 (1 H, d, J=2.42 Hz), 6.44 (1 H, dd, J=8.68, 2.53 Hz), 6.35 (1 H, s), 5.01-5.04 (2 H, m), 3.84-3.89 (3 H, m), 3.62-3.69 (2 H, m), 2.77 (2 H, td, J=12.03, 2.75 Hz), 2.58 (1 H, tt, J=11.29, 3.87 Hz), 2.21 (3 H, s), 1.99 (2 H, s), 1.80-1.91 (2 H, m).

Workup

  1. customAfter this time, the solvent was removed under reduced pressure
  2. customthe resultant residue was partitioned between EtOAc (100 mL) and water (50 mL)
  3. washThe organic phase was washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated on a rotary evaporator
  6. customto yield a residue
  7. customThe residue was purified by flash chromatography
  8. washa 40 g silica gel cartridge and gradient elution from 10:1 Hex/EtOAc to 1:1 Hex/EtOAc
  9. additionThe fractions containing the product
  10. concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record
ord-9eec83f8371646c489e19e9a697d2d22
Source dataset
uspto-grants-2013_01
Patent number
US08354432B2

Reaction notes

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