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

HRID 1804834ノート

反応式

HRID 1804834 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-9eec83f8371646c489e19e9a697d2d22
出典データセット
uspto-grants-2013_01
特許番号
US08354432B2

反応ノート

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