反応式
[H-].[Na+].[CH:3]1([O:8][C:9]2[CH:10]=[C:11]([CH:17]3[CH2:21][NH:20][C:19](=[O:22])[CH2:18]3)[CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH2:7][CH2:6][CH2:5][CH2:4]1.C1OCCOCCOCCOCCOC1.[F:38][C:39]1[C:46]([F:47])=[CH:45][CH:44]=[CH:43][C:40]=1[CH2:41]Br>CN(C)C=O.O1CCCC1.C(OCC)(=O)C>[F:38][C:39]1[C:46]([F:47])=[CH:45][CH:44]=[CH:43][C:40]=1[CH2:41][N:20]1[CH2:21][CH:17]([C:11]2[CH:12]=[CH:13][C:14]([O:15][CH3:16])=[C:9]([O:8][CH:3]3[CH2:4][CH2:5][CH2:6][CH2:7]3)[CH:10]=2)[CH2:18][C:19]1=[O:22]参加物
反応条件
- 温度
- 0 °C
実験手順
Sodium hydride (20 mg, 0.5 mmol) was added, under an atmosphere of nitrogen at room temperature, to a mixture of 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (110 mg, 0.4 mmol) and 110 μL of 15-crown-5 in 2 mL of N,N-dimethylformamide. After 3 hours, the mixture was cooled to 0° C. and 2,3-difluorobenzyl bromide (166 mg, 0.8 mmol) in 2 mL of tetrahydrofuran was added. The resulting mixture was allowed to stir at room temperature for 6 hours. 100 mL of ethyl acetate was added, followed by the addition of 100 mL of ice cold water. After standard aqueous work up, the crude product was purified by flash column chromatography (ethyl acetate/hexane 2:1) to afford 112 mg (70%) of 1-(2,3-difluorobenzyl)-4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone: 1H NMR (300 MHz, CDCl3) δ 7.18-6.98 (m, 3H), 6.79 (d, J=8.1 Hz, 1H), 6.90 (d, J=8.1 Hz, 1H), 6.68 (s, 1H) 4.71-4.69 (m, 1H), 4.60 (s, 2H), 3.81 (s, 3H), 3.68 (t, J=9.0 Hz, 1H), 3.66-3.54 (m, 1H), 3.29 (dd, J=9.6, 7.2 Hz, 1H), 2.84 (dd, J=16.8, 9.0 Hz, 1H), 2.57 (dd, J=16.8, 8.4 Hz, 1H), 2.00-1.75 (b, 6H), 1.70-1.52 (b, 2H).
後処理
- customAfter standard aqueous work up, the crude product was purified by flash column chromatography (ethyl acetate/hexane 2:1)
出典と根拠
- ORDレコード
- ord-684062a8ff4c4bceaac3981106855512
- 出典データセット
- uspto-grants-2009_09
- 特許番号
- US07585882B2
関連ノート
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