反応 #1565614

反応方程式

ethyl acetate

Iodomethane

[cis-8-hydroxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methoxy-phenyl)methanone

sodium hydride

→

(4-isopropoxy-3-methoxy-phenyl)-[cis-8-methoxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]methanone

溶媒

water

DMF

反応条件

後処理

1. 1
   workup.STIRRINGThe mixture was stirred at room temperature overnight
2. 2
   抽出The aqueous layer was extracted with ethyl acetate (2×)
3. 3
   洗浄The combined organic layers were washed with water (3×), brine
4. 4
   乾燥dried over MgSO4
5. 5
   ろ過filtered
6. 6
   濃縮concentrated to dryness
7. 7
   その他The crude material was purified by column chromatography (50-60% ethyl acetate-Hex)

実験手順

To a solution of [cis-8-hydroxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methoxy-phenyl)methanone (139 mg, 0.3 mmol) in DMF (4 mL) was added sodium hydride (34 mg, 1.5 mmol). The mixture was stirred at room temperature for 30 minutes. Iodomethane (187 μL, 3.00 mmol) was added. The mixture was stirred at room temperature overnight, then repartitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were washed with water (3×), brine, dried over MgSO4, filtered and concentrated to dryness. The crude material was purified by column chromatography (50-60% ethyl acetate-Hex) to provide (4-isopropoxy-3-methoxy-phenyl)-[cis-8-methoxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]methanone (102 mg). 1H NMR (400 MHz, CDCl3) δ 7.48-7.33 (m, 4H), 7.33-7.28 (m, 1H), 7.01-6.90 (m, 2H), 6.86 (d, J=8.2 Hz, 1H), 4.66-4.46 (m, 2H), 4.12-3.90 (m, 2H), 3.86 (s, 3H), 3.76-3.61 (m, 1H), 3.48 (s, 1H), 3.37 (d, J=4.5 Hz, 3H), 3.21 (t, J=11.8 Hz, 1H), 2.28 (dd, J=39.8, 13.2 Hz, 2H), 2.00 (dd, J=12.6, 2.7 Hz, 1H), 1.85-1.62 (m, 3H), 1.59-1.44 (m, 1H), 1.42-1.33 (m, 7H). ESI-MS m/z calc. 453.25, found 454.5 (M+1)+; Retention time: 1.65 minutes (3 minute run).

出典