Diisopropylethylamine → 2-Benzyloxy-1-[4-(2,4-dichloro-phenyl)-4-hydroxy-piperidin-1-yl]-ethanone
Reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1([OH:15])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C(N(C(C)C)CC)(C)C.[CH2:25]([O:32][CH2:33][C:34](Cl)=[O:35])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>ClCCl>[CH2:25]([O:32][CH2:33][C:34]([N:12]1[CH2:11][CH2:10][C:9]([C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])([OH:15])[CH2:14][CH2:13]1)=[O:35])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1Participants
Procedure
To a solution of 4-(2,4-dichloro-phenyl)-piperidin-4-ol (0.10 g, 0.40 mmol) in dichloromethane (2 mL) was added diisopropyl ethylamine (0.073 mL, 0.42 mmol) followed by benzyloxy acetyl chloride (0.078 g, 0.42 mmol). The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with dichloromethane (10 mL) and washed with saturated aqueous sodium bicarbonate (10 mL). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residual oil was chromatographed on silica gel using dichloromethane/methanol from 100% to 97% dichloromethane in a gradient fashion, to give the title compound as a glassy solid. The material was used as is without further purification. 1H NMR (300 MHz, CDCl3): δ 7.35 (m, 8H), 4.58 (m, 3H), 4.22 (m, 2H), 3.86 (bm, 1H), 3.57 (bm, 1H), 3.13 (bm, 1H), 2.64 (s, 1H), 2.26 (m, 2H), 1.97 (m, 2H).
Workup
- washwashed with saturated aqueous sodium bicarbonate (10 mL)
- dry with materialThe organic layer was dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residual oil was chromatographed on silica gel
Sources & evidence
- ORD record
- ord-c646fa9c457f4db4b1af4cf34ace1cd2
- Source dataset
- uspto-grants-2011_05
- Patent number
- US07935703B2
Reaction notes
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