反应详情

温度

75 °C

To [8-benzyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone hydrochloride salt (43 mg, 0.09 mmol) in DMF (0.5 mL) was added sodium hydride (11 mg, 0.30 mmol) and the reaction mixture was stirred for 20 minutes. Iodoethane (30 μL, 0.38 mmol) was added and the reaction mixture was stirred for 3 hours, then diluted with EtOAc, filtered, concentrated in vacuo. The residue was purified by silica gel column chromatography using 10-100 EtOAc/hexanes eluent to give the ether intermediate as pale yellow oil. The oil was dissolved in methanol (0.6 mL), and Pd (5 mg, 0.004 mmol) and ammonium formate (27 mg, 0.44 mmol) were added and the reaction mixture was heated at 75° C. for 40 minutes. The reaction mixture was filtered, concentrated in vacuo, diluted with ethyl acetate, washed with 1:1 3M NaOH/sat. aq. NaHCO3, dried over MgSO4, filtered and concentrated in vacuo to give [10-(ethoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (25 mg, 74%) as a pale yellow oil. ESI-MS m/z calc. 390.5. Found 391.3 (M+1)+; Retention time: 1.17 minutes (3 min run).

1. stirringthe reaction mixture was stirred for 3 hours
2. filtrationfiltered
3. concentrationconcentrated in vacuo
4. customThe residue was purified by silica gel column chromatography
5. customto give the ether intermediate as pale yellow oil
6. filtrationThe reaction mixture was filtered
7. concentrationconcentrated in vacuo
8. additiondiluted with ethyl acetate
9. washwashed with 1:1 3M NaOH/
10. dry with materialaq. NaHCO3, dried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo