Cesium carbonate → 5-[4-(1-Benzofuran-2-yl)phenyl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid

HRID 1798769Notes

Reaction equation

HRID 1798769 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH:14]([CH:18]([OH:28])[CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24](I)=[CH:23][CH:22]=1)[C:15]([OH:17])=[O:16].[O:29]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[CH:31]=[C:30]1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.[Pd]>[O:29]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[CH:31]=[C:30]1[C:24]1[CH:25]=[CH:26][C:21]([CH2:20][CH2:19][CH:18]([OH:28])[CH:14]([CH2:13][CH2:12][N:3]2[C:2](=[O:1])[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[C:4]2=[O:11])[C:15]([OH:17])=[O:16])=[CH:22][CH:23]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2776266Benzo[b]furan-2-boronic acidHCID 578870292-[2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4-iodophenyl)pentanoic acid

Product 1

HCID 117200045-[4-(1-Benzofuran-2-yl)phenyl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acidYield 12.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A solution of 2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4-iodophenyl)pentanoic acid (25 mg, 50 μmol) in dimethylformamide (1.0 mL) was added in one portion to a mixture of -benzofuran-2-ylboronic acid (11 mg, 70 μmol) and fibrecat FC1001 (2.71% Pd; 20 mg, 5.0 μmol) in a Smith microwave reaction vial. Cesium carbonate (41.0 mg, 125 μmol) was added and the vial capped. The crude reaction mixture was heated at 150° C. for 15 min using a Smith Synthesiser microwave reactor. On cooling the vial was opened and the contents partitioned between methanol/dichloromethane (10:90; 10 mL) and aqueous hydrochloric acid solution (2.0 M; 10 mL). The organic phase was separated and filtered through a Whatman 5 μM filter tube, washing the filter cake with methanol (2×1 mL). The filtrate was evaporated and the resulting residue was purified using mass directed auto-preparative reverse phase HPLC to give the title compound (3.0 mg, 12%) as a pale yellow solid. LC/MS: 3.69 min; z/e 484, calcd (M+1) 484. 1H NMR (400 MHz: DMSO-d6): 7.80 (6H), 7.65 (2H), 7.30 (5H), 3.65 (1H), 3.60 (2H), 2.75 (1H), 2.55 (1H), 2.40 (1H major), 2.25 (1H minor), 1.85 (2H), 1.65 (2H).

Workup

  1. customin a Smith microwave reaction vial
  2. customThe crude reaction mixture
  3. temperatureOn cooling the
  4. customthe contents partitioned between methanol/dichloromethane (10:90; 10 mL) and aqueous hydrochloric acid solution (2.0 M; 10 mL)
  5. customThe organic phase was separated
  6. filtrationfiltered through a Whatman 5 μM
  7. filtrationfilter tube
  8. washwashing the filter cake with methanol (2×1 mL)
  9. customThe filtrate was evaporated
  10. customthe resulting residue was purified

Sources & evidence

ORD record
ord-01c13c3a2ca0432c9c8e6bf67824bab1
Source dataset
uspto-grants-2013_01
Patent number
US08343986B2

Reaction notes

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