反応 #160215

反応方程式

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

収率 74.0%

溶媒

EtOAc

methanol

DMF

反応条件

後処理

1. 1
   workup.STIRRINGthe reaction mixture was stirred for 3 hours
2. 2
   ろ過filtered
3. 3
   濃縮concentrated in vacuo
4. 4
   その他The residue was purified by silica gel column chromatography
5. 5
   その他to give the ether intermediate as pale yellow oil
6. 6
   ろ過The reaction mixture was filtered
7. 7
   濃縮concentrated in vacuo
8. 8
   workup.ADDITIONdiluted with ethyl acetate
9. 9
   洗浄washed with 1:1 3M NaOH/
10. 10
    乾燥aq. NaHCO3, dried over MgSO4
11. 11
    ろ過filtered
12. 12
    濃縮concentrated in vacuo

実験手順

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).

出典