Water → Ethyl (2R)-4-(3-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

HRID 709270ノート

反応式

HRID 709270 の反応式
C(=O)([O-])[O-].[K+].[K+].[C:7]1(B(O)O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[F:16][C:17]1[C:18](=[O:37])[N:19]([CH2:24][CH2:25][C@@:26]([CH3:36])([S:32]([CH3:35])(=[O:34])=[O:33])[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:20]=[CH:21][C:22]=1I.O>O1CCOCC1.[Pd]>[F:16][C:17]1[C:18](=[O:37])[N:19]([CH2:24][CH2:25][C@@:26]([CH3:36])([S:32]([CH3:35])(=[O:33])=[O:34])[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:20]=[CH:21][C:22]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

参加物

7

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 67249327Ethyl (2R)-4-(3-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

生成物 1

HCID 67248709Ethyl (2R)-4-(3-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate収率 51.2%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

Pd EnCat™ (172 mg, 0.067 mmol) was added to a mixture of potassium carbonate (298 mg, 2.16 mmol), phenylboronic acid (132 mg, 1.08 mmol), and ethyl (2R)-4-(3-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate (288 mg, 0.647 mmol) in 1,4-dioxane:water (10 ml, 4:1) in a 20 ml vial. The vial was sealed and the reaction was heated to 80° C. and allowed to stir overnight at that temperature. The reaction was allowed to cool to RT, filtered and the catalyst was washed with methanol (20 mL) and dichloromethane (20 mL). The combined filtrates were concentrated and the crude product was purified via flash chromatography using an Analogix SF15-12 g column and an eluant of ethyl acetate in heptane (60-100%) to afford the title compound as a white solid (131 mg, 51.2%). LC-MS m/z 396.1 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.36 (t, J=7.12 Hz, 3H) 1.79 (s, 3H) 2.46-2.67 (m, 2H) 3.14 (s, 3H) 3.99-4.16 (m, 1H) 4.22-4.44 (m, 3H) 6.24-6.39 (m, 1H) 7.10-7.22 (m, 1H) 7.38-7.55 (m, 3H) 7.54-7.63 (m, 2H).

後処理

  1. customThe vial was sealed
  2. temperatureto cool to RT
  3. filtrationfiltered
  4. washthe catalyst was washed with methanol (20 mL) and dichloromethane (20 mL)
  5. concentrationThe combined filtrates were concentrated
  6. customthe crude product was purified via flash chromatography

出典と根拠

ORDレコード
ord-34a156fa147146c2989c8d3df02df1d5
出典データセット
uspto-grants-2015_11
特許番号
US09180123B2

反応ノート

読み込み中…