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

HRID 540458

反応式

HRID 540458 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 degased and filled back with N2. Dioxane (45 mL) and water (5 mL) were then added. The mixture was degased 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 degased
  2. additionfilled back with N2
  3. additionDioxane (45 mL) and water (5 mL) were then added
  4. customThe mixture was degased 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-822b0980017b4dbbbb0ae719a0051031
出典データセット
uspto-grants-2014_10
特許番号
US08871738B2

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