Dimethylformamide → 3-(2-Cyano-4-{2-[5-methyl-2-(4-phenoxyphenyl)oxazol-4-yl]ethoxy}phenyl)propionic acid ethyl ester

HRID 1181100Notes

Reaction equation

HRID 1181100 reaction equation
[CH2:1]([O:3][C:4](=C)[CH2:5][CH2:6][C:7]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:8]=1[C:9]#[N:10])[CH3:2].[CH3:17][C:18]1[O:22][C:21]([C:23]2[CH:28]=[CH:27][C:26]([O:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:25][CH:24]=2)=[N:20][C:19]=1[CH2:36][CH2:37]OS(C1C=CC(C)=CC=1)(=O)=O.CN(C=[O:53])C>CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:53])[CH2:5][CH2:6][C:7]1[CH:14]=[CH:13][C:12]([O:15][CH2:37][CH2:36][C:19]2[N:20]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([O:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[CH:25][CH:24]=3)[O:22][C:18]=2[CH3:17])=[CH:11][C:8]=1[C:9]#[N:10])[CH3:2]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 179843252-(3-Ethoxy-but-3-enyl)-5-hydroxy-benzonitrileHCID 59759494Toluene-4-sulfonic acid 2-[5-methyl-2-(4-phenoxy-phenyl)-oxazol-4-yl]-ethyl ester

Product 1

HCID 692321723-(2-Cyano-4-{2-[5-methyl-2-(4-phenoxyphenyl)oxazol-4-yl]ethoxy}phenyl)propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2-(3-ethoxy-but-3-enyl)-5-hydroxy-benzonitrile (220 mg, 1.00 mmol), toluene-4-sulfonic acid 2-[5-methyl-2-(4-phenoxy-phenyl)-oxazol-4-yl]-ethyl ester (450 mg, 1.00 mmol; Preparation 6), and CsCO3 (978 mg, 3.00 mmol) in DMF (10 mL) was stirred overnight at 60° C. under an N2. The mixture was cooled, diluted with EtOAc (20 mL) and washed with brine (20 mL). The organic layer was dried (Na2SO4) and concentrated. The product mixture was purified by radial chromatography (10-70% EtOAc/hexanes) to give 3-(2-cyano-4-{2-[5-methyl-2-(4-phenoxyphenyl)oxazol-4-yl]ethoxy}phenyl)propionic acid ethyl ester (201 mg). A solution of this ester in EtOH (10 mL) and 5N NaOH (10 mL) was heated at 70° C. overnight, concentrated, acidified with 1N HCl, and extracted with EtOAc. The organic layer dried (Na2SO4) and concentrated to give the title compound (192 mg); MS [ES] m/z 469 (M+1).

Workup

  1. temperatureThe mixture was cooled
  2. washwashed with brine (20 mL)
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe product mixture was purified by radial chromatography (10-70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-4fe4c4379d8c41e982f51e8494e310de
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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