Potassium Phosphate, Tribasic → 1-(4-(2-Cyclopropyl-1-oxoisoindolin-5-yl)benzyl)-3-methylimidazolidine-2,4-dione

HRID 1891256Notes

Reaction equation

HRID 1891256 reaction equation
[CH:1]1([N:4]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[C:9](B4OC(C)(C)C(C)(C)O4)[CH:10]=3)[C:5]2=[O:22])[CH2:3][CH2:2]1.Br[C:24]1[CH:38]=[CH:37][C:27]([CH2:28][N:29]2[CH2:33][C:32](=[O:34])[N:31]([CH3:35])[C:30]2=[O:36])=[CH:26][CH:25]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[CH:1]1([N:4]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[C:9]([C:24]4[CH:38]=[CH:37][C:27]([CH2:28][N:29]5[CH2:33][C:32](=[O:34])[N:31]([CH3:35])[C:30]5=[O:36])=[CH:26][CH:25]=4)[CH:10]=3)[C:5]2=[O:22])[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 594023502-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 668132201-(4-Bromobenzyl)-3-methylimidazolidine-2,4-dione

Product 1

HCID 513535561-(4-(2-Cyclopropyl-1-oxoisoindolin-5-yl)benzyl)-3-methylimidazolidine-2,4-dioneYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

2-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (1A5) (3.34 mmol, 1.0 g), 1-(4-bromobenzyI)-3-methylimidazolidine-2,4-dione (1B6) (3.34 mmol, 0.946 g), tris(dibenzylidineacetone)dipalladium (0.167 mmol, 153 mg), tricyclohexylphosphine (0.401 mmol, 112 mg) and potassium phosphate (5.68 mmol, 1.2 mg) were suspended in a mixture of dioxane (10 ml) and water (5 ml) and heated at 130° C. in the microwave for 15 min. The reaction was quenched with sat. NaHCO3 and diluted with DCM and then passed through a hydrophobic fritted tube. The combined organic layers were concentrated and the residue purified on silica eluting with 75-100% EtOAc/Heptane to afford 1-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)-3-methylimidazolidine-2,4-dione (Example 1a) (685 mg, 55%) 1H NMR (400 MHz, CDCl3) δ 7.99 (d, 1H) 7.65 (d, 1H) 7.62 (d, 2H) 7.59 (s, 1H) 7.36 (d, 2H) 4.63 (s, 2H) 4.38 (s, 2H) 3.79 (s, 2H) 3.08 (s, 3H) 2.95 (m, 1H) 0.98-0.87 (m, 4H) LCMS m/z (M+H) 376.2.

Workup

  1. customThe reaction was quenched with sat. NaHCO3
  2. additiondiluted with DCM
  3. custompassed through a hydrophobic fritted tube
  4. concentrationThe combined organic layers were concentrated
  5. customthe residue purified on silica eluting with 75-100% EtOAc/Heptane

Sources & evidence

ORD record
ord-cc143872ff7f4ccca37de05cced4dd9f
Source dataset
uspto-grants-2013_08
Patent number
US08507521B2

Reaction notes

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