反応式
F[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14].[NH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>CN(C=O)C.O>[N+:13]([C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:2]=1[N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])([O-:15])=[O:14]参加物
反応条件
- 温度
- 50 °C
実験手順
A mixture of ethyl 4-fluoro-3-nitrobenzoate (Clontech 01072, 500 mg; 2.35 mmol; 1 eq.) and piperidine (599.2 mg; 7.04 mmol; 3 eq.) in DMF (2 mL) was heated to 50° C. for 3 hours. The reaction was then allowed to return to RT and diluted with water. It was extracted with EtOAc and the organic phase was dried over sodium sulfate and concentrated in vacuo, affording ethyl 3-nitro-4-piperidin-1-ylbenzoate as a yellow oil. The residue was taken up in THF (15 mL) and lithium hydroxide (280.86 mg; 11.73 mmol; 5 eq.) was added, followed by water (15 mL). The reaction mixture was then stirred at RT for 5 hours. It was concentrated and the residue was diluted with water. The aqueous phase was washed with Et2O and acidified to pH 5 with acetic acid. It was extracted with Et2O and the organic phase was dried over magnesium sulfate and concentrated, affording the title compound as a yellow solid (562 mg, 96%). 1H NMR: (DMSO-d6, 300 MHz) δ 13.07 (s, 1H), 8.29-8.28 (d, J=2.11 Hz, 1H), 8.03-8 (dd, J=8.91 Hz, J=2.20 Hz, 1H), 7.35-7.33 (d, J=8.91 Hz, 1H), 3.15-3.13 (m, 4H), 1.64-1.60 (m, 6H). LC/MS (Method A): 252.9 (M+H)+; 250.9 (M−H)−. HPLC (Method A) Rt 3.69 min (Purity: 99.7%).
後処理
- customto return to RT
- extractionIt was extracted with EtOAc
- dry with materialthe organic phase was dried over sodium sulfate
- concentrationconcentrated in vacuo
出典と根拠
- ORDレコード
- ord-b9d6e5aeb87b4261a8c9995a8d711f38
- 出典データセット
- uspto-grants-2012_06
- 特許番号
- US08202865B2
関連ノート
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