(5BETA,17BETA)-17-羟基-17-(甲基-D3)-2'H-雄甾-2-烯并[3,2-C]吡唑-5'(1'H)-酮 → 2-(4-Fluoro-benzylidene)-3-methyl-succinic acid 1-methyl ester

HRID 238601

反应方程式

HRID 238601 反应方程式
CO.[H-].[Na+].[F:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=O)=[CH:8][CH:7]=1.C[O:15][C:16](=[O:24])[CH:17]([CH3:23])[CH2:18][C:19]([O:21][CH3:22])=[O:20]>C1(C)C=CC=CC=1>[CH3:22][O:21][C:19](=[O:20])[C:18](=[CH:10][C:9]1[CH:12]=[CH:13][C:6]([F:5])=[CH:7][CH:8]=1)[CH:17]([CH3:23])[C:16]([OH:24])=[O:15]

参与物

6

反应物 4

HCID 887(5BETA,17BETA)-17-羟基-17-(甲基-D3)-2'H-雄甾-2-烯并[3,2-C]吡唑-5'(1'H)-酮HCID 15350甲基丁二酸二甲酯HCID 24758氢化钠HCID 68023对氟苯甲醛

产物 1

HCID 667755872-(4-Fluoro-benzylidene)-3-methyl-succinic acid 1-methyl ester收率 33%

试剂、催化剂与溶剂 1

HCID 1140甲苯溶剂2 次

实验过程

After careful addition of absolute methanol (0.1 mL) to a suspension of sodium hydride (60% in mineral oil, 20 g, 0.5 mol) in anhydrous toluene (200 mL), a solution of 4-fluoro-benzaldehyde (31 g, 0.25 mol) and 2-methyl-succinic acid dimethyl ester (60 g, 0.38 mol) in anhydrous toluene (100 mL) was added at room temperature under a stream of nitrogen. The resulting mixture was stirred at room temperature for 30 minutes and then quenched by the slow addition of water (20 mL). The mixture was acidified by the addition of concentrated hydrochloric acid, and extracted with ethyl acetate (200 mL×3). The combined organic layers were dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography (elution with 30% ethyl acetate in petroleum ether) to afford 2-(4-fluoro-benzylidene)-3-methyl-succinic acid 1-methyl ester (20 g, 33%) as a white solid. 1H NMR (400 MHz, acetone-d6) δ ppm 7.77 (s, 1H), 7.54 (d, J=8.8 Hz, 2H), 7.25 (d, J=8.8 Hz, 2H), 3.82 (q, 7.2 Hz, 1H), 1.40 (d, J=6.8 Hz, 3H).

后处理

  1. customquenched by the slow addition of water (20 mL)
  2. additionThe mixture was acidified by the addition of concentrated hydrochloric acid
  3. extractionextracted with ethyl acetate (200 mL×3)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (elution with 30% ethyl acetate in petroleum ether)

来源与证据

ORD记录
ord-cc74954780564f1fbeb84ad8f3fdcd1d
来源数据集
uspto-grants-2014_02
专利号
US08642629B2

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