반응 #160215

반응 방정식

Iodoethane

ammonium formate

[8-benzyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone hydrochloride salt

sodium hydride

→

[10-(ethoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

수율 74.0%

용매

EtOAc

methanol

DMF

반응 조건

후처리

1. 1
   workup.STIRRINGthe reaction mixture was stirred for 3 hours
2. 2
   여과filtered
3. 3
   농축concentrated in vacuo
4. 4
   기타The residue was purified by silica gel column chromatography
5. 5
   기타to give the ether intermediate as pale yellow oil
6. 6
   여과The reaction mixture was filtered
7. 7
   농축concentrated in vacuo
8. 8
   workup.ADDITIONdiluted with ethyl acetate
9. 9
   세척washed with 1:1 3M NaOH/
10. 10
    건조aq. NaHCO3, dried over MgSO4
11. 11
    여과filtered
12. 12
    농축concentrated in vacuo

실험 절차

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).

출처