Cesium carbonate → 3-{2-(2-tert-Butoxycarbonylamino-ethyl)-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-propionic acid methyl ester

HRID 1181085Notes

Reaction equation

HRID 1181085 reaction equation
[CH3:1][O:2][C:3](=[O:23])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:7]=1[CH2:13][CH2:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].[CH3:24][C:25]1[O:29][C:28]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[N:27][C:26]=1[CH2:36][CH2:37]OS(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:23])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:37][CH2:36][C:26]2[N:27]=[C:28]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[O:29][C:25]=2[CH3:24])=[CH:8][C:7]=1[CH2:13][CH2:14][NH:15][C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 120517392-(5-Methyl-2-phenyloxazol-4-yl)ethyl 4-methylbenzenesulfonateHCID 589793153-[2-(2-Tert-butoxycarbonylamino-ethyl)-4-hydroxy-phenyl]-propionic acid methyl ester

Product 1

HCID 589795263-{2-(2-tert-Butoxycarbonylamino-ethyl)-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-propionic acid methyl esterYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 3-[2-(2-tert-butoxycarbonylamino-ethyl)-4-hydroxy-phenyl]-propionic acid methyl ester (0.807 g, 2.50 mmol) and toluene-4-sulfonic acid 2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl ester (1.34 g, 3.74 mmol) in DMF (5 mL) was added Cs2CO3 (1.22 g, 3.74 mmol). The suspension was stirred at 65° C. for 48 h, quenched with H2O (200 mL), and extracted with EtOAc (3×100 mL). The combined organics were dried (Na2SO4) and concentrated to a residue, which was purified on silica gel chromatography (hexanes/EtOAc 9/1 to 8/2 to 6/4) to afford the title compound as a colorless oil (0.90 g, 71%). 1H NMR (400 MHz, CDCl3): δ 1.42 (s, 9H), 2.37 (s, 3H), 2.54 (t, 2H, J=7.8 Hz), 2.77 (t, 2H, J=7.8 Hz), 2.88 (t, 2H, J=6.8 Hz), 2.96 (t, 2H, J=6.8 Hz), 3.33 (˜dt, 2H, J=6.8 Hz), 3.65 (s, 3H), 4.20 (t, 2H, J=6.8 Hz), 6.70 (br s, 1H), 6.72 (d, 1H, J=8.3 Hz), 7.05 (d, 1H, J=8.3 Hz), 7.39-7.44 (m, 3H), 7.95-7.98 (m, 2H). MS (ES+) m/z [M+H]+.

Workup

  1. customquenched with H2O (200 mL)
  2. extractionextracted with EtOAc (3×100 mL)
  3. dry with materialThe combined organics were dried (Na2SO4)
  4. concentrationconcentrated to a residue, which
  5. customwas purified on silica gel chromatography (hexanes/EtOAc 9/1 to 8/2 to 6/4)

Sources & evidence

ORD record
ord-9e18330cc9014c0197c31c302be78a71
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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