N-bromobutanimide → (E)-4-bromo-3-[4-(2-hydroxy-2-methyl-propyl)-phenoxy]-but-2-enoic acid ethyl ester

HRID 19381

反応式

HRID 19381 の反応式
[CH2:1]([O:3][C:4](=[O:20])/[CH:5]=[C:6](/[O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])=[CH:11][CH:10]=1)\[CH3:7])[CH3:2].[Br:21]N1C(=O)CCC1=O.N(C(C)(CC(C)C)C#N)=NC(C)(CC(C)C)C#N>ClCCl>[CH2:1]([O:3][C:4](=[O:20])/[CH:5]=[C:6](/[O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])=[CH:13][CH:14]=1)\[CH2:7][Br:21])[CH3:2]

参加物

5

反応物 3

HCID 67184N-bromobutanimideHCID 915372,2'-Azobis(2,4-dimethylvaleronitrile)HCID 66895133(E)-3-[4-(2-hydroxy-2-methyl-propyl)-phenoxy]-but-2-enoic acid ethyl ester

生成物 1

HCID 66895616(E)-4-bromo-3-[4-(2-hydroxy-2-methyl-propyl)-phenoxy]-but-2-enoic acid ethyl ester

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A solution of (E)-3-[4-(2-hydroxy-2-methyl-propyl)-phenoxy]-but-2-enoic acid ethyl ester (0.500 g, 1.80 mmol) in dichloromethane (40 mL) was treated with N-bromosuccinimide (0.350 g, 1.97 mmol) and 2,2′-azobis(2,4′-dimethylvaleronitrile) (0.045 g, 0.18 mmol) under nitrogen. The mixture was then refluxed for 5 h, cooled and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, 0% to 30% ethyl acetate/hexanes) to afford the intermediate (E)-4-bromo-3-[4-(2-hydroxy-2-methyl-propyl)-phenoxy]-but-2-enoic acid ethyl ester. A solution of (E)-4-bromo-3-[4-(2-hydroxy-2-methyl-propyl)-phenoxy]-but-2-enoic acid ethyl ester in acetonitrile (20 mL) was immediately treated with (L)-leucine methyl ester hydrochloride (0.21 g, 2.17 mmol) and N,N-diisopropylethylamine (0.510 g, 3.95 mmol). The resulting mixture was sealed in a tube and heated at 90° C. overnight and then cooled and partitioned between ethyl acetate and water. The organic layer was collected, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in tetrahydrofuran (approximately 5 mL) and heated at 160° C., for 6 h in a sealed tube. At this time, the reaction was cooled to room temperature and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, 30% to 100% ethyl acetate/hexanes) to afford, (S)-2-{4-[4-(2-hydroxy-2-methyl-propyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid methyl ester (0.180 g, 27%) as a waxy off-white solid.

後処理

  1. temperatureThe mixture was then refluxed for 5 h
  2. temperaturecooled
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash column chromatography (silica gel, 0% to 30% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-2e015e8881d34ab8ae7140903b17b2e2
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

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