2-(4-{2-[2-(4-Bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester → 2-(4-{2-[2-(4-Cyanophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic Acid Ethyl Ester

HRID 1609932Notes

Reaction equation

HRID 1609932 reaction equation
[CH2:1]([O:3][C:4](=[O:31])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][C:27](Br)=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][CH:10]=1)([CH3:7])[CH3:6])[CH3:2].[Cu][C:33]#[N:34]>CN(C)C=O.[Cu]I>[CH2:1]([O:3][C:4](=[O:31])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][C:27]([C:33]#[N:34])=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][CH:10]=1)([CH3:7])[CH3:6])[CH3:2]

Participants

5

Reactant 2

HCID 110273422-(4-{2-[2-(4-Bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl esterHCID 178418546HCID 178418546, compound

Product 1

HCID 235900232-(4-{2-[2-(4-Cyanophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic Acid Ethyl EsterYield 87%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

2-(4-{2-[2-(4-Bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester (170 mg, 0.35 mmol), copper (I) cyanide (96 mg, 1.07 mmol), and copper (I) iodide (120 mg, 0.63 mmol) were dissolved in dimethylformamide (1.5 mL) and heated to 150° C. for 20 h. The mixture was cooled ambient temperature and partitioned between EtOAc (20 mL) and saturated aqueous FeCl3 (20 mL). The organic phase was washed with FeCl3 solution, H2O, brine and then dried (MgSO4), filtered and concentrated. The product was purified by flash chromatography (15 mL SiO2, 40% EtOAc/hexanes) and obtained as a clear, colorless oil (132 mg, 87%). Rf=0.32 in 35% EtOAc/hexanes; 1H NMR (400 MHz, CDCl3) δ 8.04 (d, J=8.4 Hz, 2H), 7.69 (d, J=8.4 Hz, 2H), 6.81-6.76 (m, 4H), 4.21 (q, J=6.4 Hz, 2H), 4.18 (t, J=6.4 Hz, 2H), 2.95 (t, J=6.4 Hz, 2H), 2.38 (s, 3H), 1.51 (s, 6H), 1.26 (t, J=7.2 Hz, 3H); MS (EI) 457.2 (M+Na)+; 435.2 (M+H)+.

Workup

  1. temperatureThe mixture was cooled ambient temperature
  2. custompartitioned between EtOAc (20 mL) and saturated aqueous FeCl3 (20 mL)
  3. washThe organic phase was washed with FeCl3 solution, H2O, brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was purified by flash chromatography (15 mL SiO2, 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d476dec8d271468e83dbcc46b073c23d
Source dataset
uspto-grants-2006_01
Patent number
US06982278B2

Reaction notes

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