Hydrochloric Acid → 5-Chloro-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoic acid

HRID 1849803ノート

反応式

HRID 1849803 の反応式
O1[C:5]2([CH2:10][CH2:9][CH:8]([O:11][C:12]3[C:20]([Cl:21])=[CH:19][C:15]([C:16]([OH:18])=[O:17])=[C:14]([F:22])[CH:13]=3)[CH2:7][CH2:6]2)[O:4]CC1.Cl>CC(C)=O.[Cl-].[Na+].O>[Cl:21][C:20]1[C:12]([O:11][CH:8]2[CH2:9][CH2:10][C:5](=[O:4])[CH2:6][CH2:7]2)=[CH:13][C:14]([F:22])=[C:15]([CH:19]=1)[C:16]([OH:18])=[O:17]

参加物

5

反応物 2

HCID 313Hydrochloric AcidHCID 867036854-(1,4-Dioxaspiro[4.5]decan-8-yloxy)-5-chloro-2-fluorobenzoic acid

生成物 1

HCID 867036865-Chloro-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoic acid収率 45%

試薬・触媒・溶媒 2

HCID 180Acetone溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

To a solution of 4-(1,4-dioxaspiro[4.5]decan-8-yloxy)-5-chloro-2-fluorobenzoic acid (2.95 g, 8.92 mmol) in acetone (100 mL) was added 3 M hydrochloric acid (80 mL). The solution was heated to reflux for 17 hours and cooled to ambient temperature. The mixture was diluted with brine (200 mL) and extracted with ethyl acetate (3×150 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to dryness. The residue was purified by column chromatography with a gradient of a solution of 0.2% acetic acid in ethyl acetate and hexanes from 0-50% to afford the title compound as a colorless solid (1.14 g, 45%): 1H NMR (300 MHz, CDCl3) δ 8.07 (d, J=7.6 Hz, 1H), 6.77 (d, J=11.9 Hz, 1H), 4.82 (br s, 1H), 2.81-2.70 (m, 2H), 2.41-2.35 (m, 4H), 2.15-2.03 (m, 2H) (OH not observed); MS (ES−) m/z 285.1, 287.1 (M−1).

後処理

  1. temperatureThe solution was heated
  2. temperatureto reflux for 17 hours
  3. extractionextracted with ethyl acetate (3×150 mL)
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to dryness
  7. customThe residue was purified by column chromatography with a gradient of a solution of 0.2% acetic acid in ethyl acetate and hexanes from 0-50%

出典と根拠

ORDレコード
ord-897044bf85b346299e4bd12275263784
出典データセット
uspto-grants-2015_02
特許番号
US08952169B2

反応ノート

読み込み中…