Cesium carbonate → 2-Methyl-2-{4-[2-(5-methyl-2-biphenyl-4-yl-oxazol-4-yl)ethoxy]phenoxy}propionic acid ethyl ester

HRID 2417026Notes

Reaction equation

HRID 2417026 reaction equation
[C:1]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:6]=[CH:5][C:4]([C:7]2[O:8][C:9]([CH3:25])=[C:10]([CH2:12][CH2:13][O:14]S(C3C=CC(C)=CC=3)(=O)=O)[N:11]=2)=[CH:3][CH:2]=1.[CH2:32]([O:34][C:35](=[O:47])[C:36]([O:39][C:40]1[CH:45]=[CH:44][C:43](O)=[CH:42][CH:41]=1)([CH3:38])[CH3:37])[CH3:33].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH2:32]([O:34][C:35](=[O:47])[C:36]([CH3:38])([O:39][C:40]1[CH:45]=[CH:44][C:43]([O:14][CH2:13][CH2:12][C:10]2[N:11]=[C:7]([C:4]3[CH:5]=[CH:6][C:1]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[CH:2][CH:3]=3)[O:8][C:9]=2[CH3:25])=[CH:42][CH:41]=1)[CH3:37])[CH3:33]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 181741Ethyl 2-(4-hydroxyphenoxy)-2-methylpropanoateHCID 12966835Toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-methyl-oxazol-4-yl)ethyl ester

Product 1

HCID 112370922-Methyl-2-{4-[2-(5-methyl-2-biphenyl-4-yl-oxazol-4-yl)ethoxy]phenoxy}propionic acid ethyl esterYield 47%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of toluene-4-sulfonic acid 2-(2-biphenyl-4-yl—methyl-oxazol-4-yl)ethyl ester (14.9 g, 34.3 mmol), 2-(4-hydroxyphenoxy)-2-methyl propionic acid ethyl ester (American Home Products U.S. Pat. No. 3,795,691 (6.15 g, 27.4 mmol) and Cs2CO3 (12.0 g, 36.8 mmol) was heated at 55° C. in DMF (110 mL) for 18 h. The reaction was partitioned between ethyl acetate (160 mL) and H2O (180 mL), and the aqueous phase extracted with ethyl acetate (150 mL). The combined organic phases were dried (MgSO4) and concentrated under reduced pressure to an oil which was purified by column chromatography (600 mL SiO2, 10% ethyl acetate/hexanes to 20% ethyl acetate/hexanes) to provide 2-methyl-2-{4-[2-(5-methyl-2-biphenyl-4-yl-oxazol-4-yl)ethoxy]phenoxy}propionic acid ethyl ester (6.25 g, 47%) as a colorless, viscous oil: Rf=0.48 in 35% ethyl acetate/hexanes; 1H NMR (500 MHz, CDCl3) δ 8.05-8.03 (m, 2H), 7.67-7.64 (m, 4H), 7.46 (m, 2H), 7.38 (m, 1H), 6.83-6.77 (m, 4H), 4.22 (q, J=9.2 Hz, 2H), 4.18 (t, J=8.8 Hz, 2H), 2.97 (t, J=8.8 Hz, 2H), 2.37 (s, 3H), 1.52 (s, 6H), 1.27 (t, J=9.2 Hz, 3H).

Workup

  1. customThe reaction was partitioned between ethyl acetate (160 mL) and H2O (180 mL)
  2. extractionthe aqueous phase extracted with ethyl acetate (150 mL)
  3. dry with materialThe combined organic phases were dried (MgSO4)
  4. concentrationconcentrated under reduced pressure to an oil which
  5. customwas purified by column chromatography (600 mL SiO2, 10% ethyl acetate/hexanes to 20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-c20e8848d6804912b935373213e4b15d
Source dataset
uspto-grants-2004_11
Patent number
US06825222B2

Reaction notes

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