2-Butene, 1,4-dibromo- → 2-(4-Bromo-but-2-enyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic acid methyl ester

HRID 33616

反応式

HRID 33616 の反応式
[CH3:1][C:2]1[C:7]2[CH2:8][O:9][C:10](=[O:11])[C:6]=2[C:5]([OH:12])=[C:4]([CH2:13]/[CH:14]=[C:15](/[CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])\[CH3:16])[C:3]=1[O:23][CH3:24].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Br:35][CH2:36][CH:37]=[CH:38][CH2:39]Br>C1COCC1>[CH3:22][O:21][C:19](=[O:20])[CH:18]([CH2:39][CH:38]=[CH:37][CH2:36][Br:35])[CH2:17][C:15]([CH3:16])=[CH:14][CH2:13][C:4]1[C:5]([OH:12])=[C:6]2[C:7](=[C:2]([CH3:1])[C:3]=1[O:23][CH3:24])[CH2:8][O:9][C:10]2=[O:11]

参加物

5

反応物 3

HCID 131802-Butene, 1,4-dibromo-HCID 2724254Sodium bis(trimethylsilyl)amideHCID 6478685Methyl (4E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate

生成物 1

HCID 670102042-(4-Bromo-but-2-enyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic acid methyl ester収率 78.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-30 °C

実験手順

To a cooled (−78° C.) solution of mycophenolic acid methyl ester 159A (138 mg, 0.41 mmol) in THF (2.5 mL) was added a THF solution of sodium bis(trimethysilyl)amide (1.0 M, 0.98 mL). After stirring for 30 minutes, a solution of 1,4-dibromo-2-butene (950 mg, 4.1 mmol) in THF (2.5 mL) was added and stirring was continued for 10 minutes. The resulting mixture was warmed to −30° C. and stored at this temperature for 16 hours. The reaction was quenched with saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate to give, after evaporation of the solvent, a residue which was purified by chromatography on silica gel eluting with ethyl acetate (0% to 40%)/hexanes, affording 2-(4-bromo-but-2-enyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic acid methyl ester 159B (150 mg, 78%) as an oil; 1H NMR (300 MHz, CDCl3) δ 1.75 (s, 3H), 2.0-2.4 (m, 8H), 2.62 (m, 1H), 3.37 (d, J=6.6 Hz, 2H), 3.58 (s, 3H), 3.76 (s, 3H), 3.88 (d, J=4.8 Hz, 2H), 5.1-5.3 (m, 3H), 5.67 (brs, 2H), 7.67 (s, 1H) ppm.

後処理

  1. stirringstirring
  2. waitwas continued for 10 minutes
  3. waitstored at this temperature for 16 hours
  4. customThe reaction was quenched with saturated aqueous ammonium chloride
  5. extractionThe mixture was extracted with ethyl acetate
  6. customto give
  7. customafter evaporation of the solvent
  8. customa residue which was purified by chromatography on silica gel eluting with ethyl acetate (0% to 40%)/hexanes

出典と根拠

ORDレコード
ord-d02c6a4de90c49e9bf09acc74e0332c2
出典データセット
uspto-grants-2008_09
特許番号
US07429565B2

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