反応 #306964

反応方程式

ethyl 4-fluoro-3-nitrobenzoate

2-methylpiperidine

→

ethyl 4-(2-methylpiperidin-1-yl)-3-nitrobenzoate

溶媒

water

DMF

反応条件

後処理

1. 1
   その他to return to RT
2. 2
   抽出It was extracted with EtOAc
3. 3
   乾燥the organic phase was dried over sodium sulfate
4. 4
   濃縮concentrated in vacuo

実験手順

A mixture of ethyl 4-fluoro-3-nitrobenzoate (Clontech 01072, 1 g; 4.69 mmol; 1 eq.) and 2-methylpiperidine (1.395 g; 14.07 mmol; 3 eq.) in DMF (4 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 4-(2-methylpiperidin-1-yl)-3-nitrobenzoate as a yellow oil. The residue was taken up in THF (10 mL) and lithium hydroxide (561.73 mg; 23.46 mmol; 5 eq.) was added followed by water (10 mL). The reaction mixture was stirred at RT for 16 hours. It was concentrated and the residue was diluted with water and washed with Et2O. The aqueous layer was 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 (1.17 g, 94%). 1H NMR: (DMSO-d6, 300 MHz) δ 13.07 (s, 1H), 8.23-8.22 (d, J=2.13 Hz, 1H), 8.04-8 (dd, J=8.96 Hz, J=2.28 Hz, 1H), 7.44-7.41 (d, J=8.88 Hz, 1H), 3.64-3.60 (m, 1H), 3.25-3.17 (m, 1H), 2.90-2.84 (m, 1H), 1.82-1.43 (m, 6H), 1.06-1.04 (d, J=6.43 Hz, 3H). LC/MS (Method A): 265.0 (M+H)+; 263.0 (M−H)−.

出典