3-Chloro-4-methoxybenzeneboronic acid → (2S,3S)-tert-butyl 3-(3-chloro-4-methoxyphenyl)-2-methyl-5-oxopyrrolidine-1-carboxylate

HRID 529717

反応式

HRID 529717 の反応式
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[CH3:13][C@H:14]1[CH:18]=[CH:17][C:16](=[O:19])[N:15]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].F.[K]>>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:18]2[CH2:17][C:16](=[O:19])[N:15]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:14]2[CH3:13])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]

参加物

4

反応物 3

HCID 32475223-Chloro-4-methoxybenzeneboronic acidHCID 14736431tert-butyl (2S)-2-methyl-5-oxo-2,5-dihydro-1H-pyrrole-1-carboxylateHCID 53443437Potassium fluoride, 99%, spray-dried

生成物 1

HCID 86682281(2S,3S)-tert-butyl 3-(3-chloro-4-methoxyphenyl)-2-methyl-5-oxopyrrolidine-1-carboxylate収率 49.3%

反応条件

温度
60 °C

実験手順

To a 100 mL RBF were added (3-chloro-4-methoxyphenyl)boronic acid (1.89 g, 10.14 mmol), (S)-tert-butyl 2-methyl-5-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate (1 g, 5.07 mmol), hydroxy(cyclooctadiene)rhodiumRhodium(I) dimer (0.116 g, 0.254 mmol), potassium hydrogen fluoride (1.58 g, 20.28 mmol). The mixture was degassed and filled back with N2. Dioxane (45 mL) and water (5 mL) were then added. The mixture was degassed again and filled with N2. The reaction mixture was heated at 60° C. overnight. It was diluted with EtOAc (200 mL), washed with water, brine. Organic layer was dried over Na2SO4, and concentrated. The residue was purified by silica gel chromatography, eluted with 30% EtOAc/Hexane to give (2S,3S)-tert-butyl 3-(3-chloro-4-methoxyphenyl)-2-methyl-5-oxopyrrolidine-1-carboxylate (intermediate J1, 0.85 g) as white crystalline solid. 1H NMR (500 MHz, CDCl3): δ 7.20 (s, 1H), 7.05 (d, 1H), 6.87 (d, 1H), 4.08 (m, 1H), 3.86 (s, 3H), 2.95 (m, 2H), 2.53 (m, 1H), 1.52 (s, 9H), 1.41 (d, 3H).

後処理

  1. customThe mixture was degassed
  2. additionfilled back with N2
  3. additionDioxane (45 mL) and water (5 mL) were then added
  4. customThe mixture was degassed again
  5. additionfilled with N2
  6. additionIt was diluted with EtOAc (200 mL)
  7. washwashed with water, brine
  8. dry with materialOrganic layer was dried over Na2SO4
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography
  11. washeluted with 30% EtOAc/Hexane

出典と根拠

ORDレコード
ord-0ee9c41ec24c4d019fca48f79f176eb6
出典データセット
uspto-grants-2016_05
特許番号
US09346825B2

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