Potassium Phosphate, Tribasic → HCID 52932327, compound

HRID 1891264Notes

Reaction equation

HRID 1891264 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:37]=[CH:36][C:27]([CH2:28][N:29]2[CH2:33][C@@H:32]([CH3:34])[O:31][C:30]2=[O:35])=[CH:26][CH:25]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl>[CH:1]1([N:4]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[C:9]([C:24]4[CH:37]=[CH:36][C:27]([CH2:28][N:29]5[CH2:33][C@@H:32]([CH3:34])[O:31][C:30]5=[O:35])=[CH:26][CH:25]=4)[CH:10]=3)[C:5]2=[O:22])[CH2:2][CH2:3]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 594023502-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 67173154HCID 67173154, compound

Product 1

HCID 52932327HCID 52932327, compoundYield 36%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

2-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (1A5) (0.204 mmol, 60.9 mg) was mixed with (R)-3-(4-bromobenzyl)-5-methyloxazolidin-2-one (5F3) (0.185 mmol, 50 mg), tricyclohexylphosphine (0.022 mmol, 8.5 mg), tris(dibenzylidineacetone) dipalladium (0.009 mmol, 8.5 mg) and potassium phosphate (0.315 mmol, 66.7 mg) in dioxane (1mI) and water (0.5 ml). The mixture was heated to 130° C. for 10 minutes in the microwave before addition of DCM (3 ml) and water (2 ml). The phases were mixed and the organic phase collected using a hydrophobic fritted tube and concentrated under reduced pressure. Purification was achieved using basic HPLC to afford (R)-3-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)-5-methyloxazolid in-2-one (Example 5a) 24.1 mg (36%); 1H NMR (400 MHz, CDCl3) δ 7.88 (d, 1H) 7.66 (d, 1H) 7.59 (m, 3H) 7.38 (d, 2H) 4.64 (m, 1H) 4.51-4.41 (m, 2H) 4.37 (s, 2H) 3.54 (m, 1H) 3.03 (m, 1H) 2.97 (m, 1H) 1.43 (d, 3H) 0.95-0.89 (m, 4H) m/z (M+H) 363.2.

Workup

  1. additionThe phases were mixed
  2. customthe organic phase collected
  3. concentrationconcentrated under reduced pressure
  4. customPurification

Sources & evidence

ORD record
ord-053465a43eb9455e9b6a69e33fb95b5f
Source dataset
uspto-grants-2013_08
Patent number
US08507521B2

Reaction notes

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