Potassium tert-butoxide → Methyl 5-chloro-2-fluoro-4-((4-methylenecyclohexyl)oxy)benzoate

HRID 1849916ノート

反応式

HRID 1849916 の反応式
[CH3:1]C(C)([O-])C.[K+].[Cl:7][C:8]1[C:9]([O:19][CH:20]2[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]2)=[CH:10][C:11]([F:18])=[C:12]([CH:17]=1)[C:13]([O:15][CH3:16])=[O:14]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1.O>[Cl:7][C:8]1[C:9]([O:19][CH:20]2[CH2:25][CH2:24][C:23](=[CH2:1])[CH2:22][CH2:21]2)=[CH:10][C:11]([F:18])=[C:12]([CH:17]=1)[C:13]([O:15][CH3:16])=[O:14]

参加物

6

反応物 2

HCID 23665647Potassium tert-butoxideHCID 86703687Methyl 5-chloro-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoate

生成物 1

HCID 86703796Methyl 5-chloro-2-fluoro-4-((4-methylenecyclohexyl)oxy)benzoate収率 83.3%

試薬・触媒・溶媒 3

HCID 74505Methyltriphenyliphosphonium bromide触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
0 °C

実験手順

To a suspension of methyltriphenylphosphonium bromide (1.61 g, 4.51 mmol) in anhydrous tetrahydrofuran (20 mL) was added a solution of potassium tert-butoxide (0.541 g, 4.82 mmol) in anhydrous tetrahydrofuran (15 mL) dropwise over 3 minutes at 0° C. The mixture was stirred under a nitrogen atmosphere at 0° C. for 1 h. To this solution was added a solution of methyl 5-chloro-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoate (1.05 g, 3.48 mmol) in anhydrous tetrahydrofuran (15 mL) dropwise over 3 minutes. The mixture was stirred at ambient temperature for 21 h, then diluted with water (200 mL). The mixture was extracted with ethyl acetate (200 mL) and the organic phase was washed with water (50 mL) and brine (150 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography with a gradient of 0-10% ethyl acetate in hexanes to afford the title compound as a colorless syrup (0.866 g, 83% yield): 1H NMR (300 MHz, CDCl3) δ 7.94 (d, J=7.7 Hz, 1H), 6.67 (d, J=12.2 Hz, 1H), 4.68 (s, 2H), 4.56-4.50 (m, 1H), 3.87 (s, 3H), 2.48-2.40 (m, 2H), 2.17-2.09 (m, 2H), 1.92-1.86 (m, 4H); MS (ES+) m/z 299.00 (M+1).

後処理

  1. stirringThe mixture was stirred at ambient temperature for 21 h
  2. extractionThe mixture was extracted with ethyl acetate (200 mL)
  3. washthe organic phase was washed with water (50 mL) and brine (150 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography with a gradient of 0-10% ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-6ecaa4680b5f47b990b39ed4ace75ac4
出典データセット
uspto-grants-2015_02
特許番号
US08952169B2

反応ノート

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