Water → 1-{1-[2-Ethyl-5-(ethyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazine

HRID 419594ノート

反応式

HRID 419594 の反応式
[CH2:1]([C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6]([O:12][CH2:13][CH3:14])=[CH:5][C:4]=1F)[CH3:2].[CH3:16][S:17]([N:20]1[CH2:25][CH2:24][N:23]([CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH2:22][CH2:21]1)(=[O:19])=[O:18].C([O-])([O-])=O.[K+].[K+].O>CS(C)=O>[CH2:1]([C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6]([O:12][CH2:13][CH3:14])=[CH:5][C:4]=1[N:29]1[CH2:28][CH2:27][CH:26]([N:23]2[CH2:24][CH2:25][N:20]([S:17]([CH3:16])(=[O:19])=[O:18])[CH2:21][CH2:22]2)[CH2:31][CH2:30]1)[CH3:2]

参加物

6

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 282710281-(Methylsulfonyl)-4-(4-piperidinyl)piperazineHCID 594528781-Ethoxy-4-ethyl-5-fluoro-2-nitrobenzene

生成物 1

HCID 594527591-{1-[2-Ethyl-5-(ethyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazine収率 33.4%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
90 °C

実験手順

A mixture of 1-ethyl-4-(ethyloxy)-2-fluoro-5-nitrobenzene (Example 208, step A) (0.80 g, 3.75 mmol), 1-(methylsulfonyl)-4-(4-piperidinyl)piperazine (0.928 g, 3.75 mmol) and K2CO3 (0.622 g, 4.50 mmol) in DMSO (20 mL) was heated at 90° C. for 48 h. The reaction had not progressed sufficiently so the reaction was then heated at 120° C. for an additional 4 h. The reaction was cooled to rt, poured into H2O and extracted exhaustively with DCM. The combined organics were washed with H2O then dried over MgSO4. The resultant solution was concentrated onto silica and purified by flash chromatography to afford 1-{1-[2-ethyl-5-(ethyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazine (0.551 g, 33%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.75 (s, 1H), 6.74 (s, 1H), 4.19 (q, J=6.93 Hz, 2H), 3.19-3.28 (m, 2H), 3.06-3.14 (m, 4H), 2.87 (s, 3H), 2.52-2.79 (m, 9H), 1.80-1.92 (m, 2H), 1.46-1.67 (m, 2H), 1.33 (t, J=6.97 Hz, 3H), 1.19 (t, J=7.47 Hz, 3H).

後処理

  1. temperaturewas then heated at 120° C. for an additional 4 h
  2. temperatureThe reaction was cooled to rt
  3. extractionextracted exhaustively with DCM
  4. washThe combined organics were washed with H2O
  5. dry with materialthen dried over MgSO4
  6. concentrationThe resultant solution was concentrated onto silica
  7. custompurified by flash chromatography

出典と根拠

ORDレコード
ord-bef2f226c05d45dd9c5d04d3e3acea88
出典データセット
uspto-grants-2012_01
特許番号
US08093239B2

反応ノート

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