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Hydrochloric Acid → 4-{1-[4-Amino-3-(methyloxy)phenyl]-4-piperidinyl}-1-(2-fluoroethyl)-2-piperazinone

HRID 419445
ノート
印刷プレビュー

反応式

HRID 419445 の反応式
[F:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[C:18]([O:25][CH3:26])[CH:17]=3)[CH2:12][CH2:11]2)[CH2:6][C:5]1=[O:27].[Sn](Cl)Cl.Cl>O1CCOCC1>[NH2:22][C:19]1[CH:20]=[CH:21][C:16]([N:13]2[CH2:12][CH2:11][CH:10]([N:7]3[CH2:8][CH2:9][N:4]([CH2:3][CH2:2][F:1])[C:5](=[O:27])[CH2:6]3)[CH2:15][CH2:14]2)=[CH:17][C:18]=1[O:25][CH3:26]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 24479Stannous ChlorideHCID 594526081-(2-Fluoroethyl)-4-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-2-piperazinone

生成物 1

HCID 594527794-{1-[4-Amino-3-(methyloxy)phenyl]-4-piperidinyl}-1-(2-fluoroethyl)-2-piperazinone収率 91%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
0 °C

実験手順

1-(2-Fluoroethyl)-4-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-2-piperazinone (0.832 g, 2.19 mmol) was dissolved in 50 mL of dioxane with stirring and cooled to 0° C. Tin(II) chloride (1.66 g, 8.76 mmol) in concentrated HCl (37%, 15.0 mL, 167 mmol) was added dropwise via pipet. The reaction was warmed to rt and stirred overnight. The reaction was quenched by the slow addition of 6N NaOH solution until the pH was greater than 10. The mixture was extracted with EtOAc, and the organic layer was washed with brine. The combined aqueous layers were extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford 0.695 g (91%) of the title compound of step C. 1H NMR (400 MHz, DMSO-d6) δ 6.50-6.40 (m, 2H), 6.25 (dd, J=8.4, 2.0 Hz, 1H), 4.56 (t, J=4.9 Hz, 1H), 4.44 (t, J=4.9 Hz, 1H), 4.15 (br. s., 2H), 3.69 (s, 3H), 3.58 (t, J=4.9 Hz, 1H), 3.52 (t, J=4.9 Hz, 1H), 3.44-3.33 (m, 2H), 3.32-3.23 (m, 2H), 3.10 (s, 2H), 2.69 (t, J=5.4 Hz, 2H), 2.52-2.39 (m, 2H), 2.32-2.20 (m, 1H), 1.74-1.86 (m, 2H), 1.39-1.55 (m, 2H).

後処理

  1. temperatureThe reaction was warmed to rt
  2. stirringstirred overnight
  3. customThe reaction was quenched by the slow addition of 6N NaOH solution until the pH was greater than 10
  4. extractionThe mixture was extracted with EtOAc
  5. washthe organic layer was washed with brine
  6. extractionThe combined aqueous layers were extracted with EtOAc
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography

出典と根拠

ORDレコード
ord-f7a3490ae8554f7f8d58c8356705ae31
出典データセット
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08093239B2

反応ノート

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