反応 #1565622

反応方程式

sodium bicarbonate

cyclopropylmethyl bromide

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

sodium hydride

→

(4-isopropoxy-3-methylphenyl)methanone

溶媒

ethyl acetate

water

DMF

反応条件

後処理

1. 1
   workup.STIRRINGto stir overnight at room temperature
2. 2
   乾燥The organic layer was dried over sodium sulfate
3. 3
   ろ過filtered
4. 4
   濃縮concentrated under reduced pressure
5. 5
   その他The crude material was purified by column chromatography

実験手順

To [cis-8-hydroxy-10-(3-pyridyl)-11-oxa-3-azaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (80 mg) in DMF at 0° C. was added sodium hydride (5 eq., 60 wt % in mineral oil). After stirring at room temperature for 5 minutes, the cyclopropylmethyl bromide (5 eq.) was added. The reaction mixture was allowed to stir overnight at room temperature. The reaction mixture was stirred with saturated sodium bicarbonate solution (20 mL). The mixture was repartitioned between water (50 mL) and ethyl acetate (50 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to provide cis-4-(cyclopropylmethoxy)-2-(pyridin-3-yl)-1-oxa-9-azaspiro[5.5]undecan-9-yl)(4-isopropoxy-3-methylphenyl)methanone. 1H NMR (400 MHz, CDCl3) δ 8.62 (s, 1H), 8.55 (d, J =3.9 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.30 (dd, J=7.8, 4.8 Hz, 1H), 7.23-7.11 (m, 2H), 6.80 (d, J=8.2 Hz, 1H), 4.70-4.51 (m, 1H), 4.56 (dq, J=12.1, 6.1 Hz, 1H), 4.37 (br s, 1H), 3.82-3.00 (m, 5H), 3.34 (d, J=6.8 Hz, 1H), 2.40-2.10 (m, 2H), 2.19 (s, 3H), 2.09-1.92 (m, 2H), 1.88-1.39 (m, 4H), 1.42-1.26 (m, 6H), 1.04 (td, J=7.0, 3.5 Hz, 1H), 0.64-0.47 (m, 2H), 0.30-0.12 (m, 2H).

出典