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

HRID 529717Notes

Reaction equation

HRID 529717 reaction equation
[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]

Participants

4

Reactant 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

Product 1

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

Conditions

Temperature
60 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-0ee9c41ec24c4d019fca48f79f176eb6
Source dataset
uspto-grants-2016_05
Patent number
US09346825B2

Reaction notes

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