Methane → 3-(4-Fluorophenyl)-1-methyl-1-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yloxy)urea

HRID 1895925ノート

反応式

HRID 1895925 の反応式
[CH3:1][NH:2][O:3][CH:4]1[CH2:9][CH2:8][N:7]([S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)(=[O:12])=[O:11])[CH2:6][CH2:5]1.ClC([O:26][C:27](Cl)(Cl)Cl)=O.C.[F:32][C:33]1[CH:39]=[CH:38][C:36]([NH2:37])=[CH:35][CH:34]=1.C(N(CC)C(C)C)(C)C>O1CCCC1>[F:32][C:33]1[CH:39]=[CH:38][C:36]([NH:37][C:27](=[O:26])[N:2]([CH3:1])[O:3][CH:4]2[CH2:5][CH2:6][N:7]([S:10]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:20])[F:21])[CH:14]=3)(=[O:12])=[O:11])[CH2:8][CH2:9]2)=[CH:35][CH:34]=1

参加物

7

反応物 5

HCID 297MethaneHCID 97314-FluoroanilineHCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 86652730N-methyl-O-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yl)hydroxylamine

生成物 1

HCID 866527313-(4-Fluorophenyl)-1-methyl-1-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yloxy)urea収率 49%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of N-methyl-O-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yl)hydroxylamine (130 mg, 0.384 mmol) in tetrahydrofuran (10 ml) was added to a suspension of trichloromethyl chloroformate (91.3 mg, 0.46 mmol) and activated charcoal (20 mg) in tetrahydrofuran (35 ml) at 0° C. over 30 minutes. After stirring at room temperature for 18 hours, the reaction mixture was filtered over silicagel and the filtrate was concentrated in vacuo. The residue was dissolved in tetrahydrofuran (15 ml), 4-fluoroaniline (65 mg, 1.13 mmol) and N,N-diisopropylethylamine (148 mg, 1.15 mmol) were added and the whole was stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo and the residue was diluted with ethyl acetate (50 ml), washed with H2O (20 ml×2), brine (20 ml×2), dried over Na2SO4 and concentrated in vacuo. The residual solid was recrystallized from diethyl ether to give 3-(4-fluorophenyl)-1-methyl-1-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yloxy)urea (89.5 mg, 49%) as a white solid. LCMS: 476 [M+1]+. 1H NMR (DMSO-d6) δ: 1.79 (m, 2H), 1.98 (m, 2H), 2.59 (m, 2H), 3.0 (s, 3H), 3.62 (d, 2H), 3.89 (m, 1H), 7.11 (t, 2H), 7.50 (m, 2H), 7.94 (q, 2H), 8.12 (q, 2H), 8.70 (s, 1H).

後処理

  1. filtrationthe reaction mixture was filtered over silicagel
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe residue was dissolved in tetrahydrofuran (15 ml)
  4. stirringthe whole was stirred at room temperature for 18 hours
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. additionthe residue was diluted with ethyl acetate (50 ml)
  7. washwashed with H2O (20 ml×2), brine (20 ml×2)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe residual solid was recrystallized from diethyl ether

出典と根拠

ORDレコード
ord-5536c3b488614e68b9c38278af3bed00
出典データセット
uspto-grants-2013_08
特許番号
US08518934B2

反応ノート

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