Cesium carbonate → 2-(4-{2-[2-(4-Bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester

HRID 2228976Notes

Reaction equation

HRID 2228976 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:26])=[C:11]([CH2:13][CH2:14][O:15]S(C3C=CC(C)=CC=3)(=O)=O)[N:12]=2)=[CH:4][CH:3]=1.[CH2:27]([O:29][C:30](=[O:42])[C:31]([O:34][C:35]1[CH:40]=[CH:39][C:38](O)=[CH:37][CH:36]=1)([CH3:33])[CH3:32])[CH3:28].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH2:27]([O:29][C:30](=[O:42])[C:31]([O:34][C:35]1[CH:40]=[CH:39][C:38]([O:15][CH2:14][CH2:13][C:11]2[N:12]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=3)[O:9][C:10]=2[CH3:26])=[CH:37][CH:36]=1)([CH3:33])[CH3:32])[CH3:28]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 181741Ethyl 2-(4-hydroxyphenoxy)-2-methylpropanoateHCID 58979135Toluene-4-sulfonic acid 2-[2-(4-bromophenyl)-5-methyloxazol-4-yl]ethyl ester

Product 1

HCID 110273422-(4-{2-[2-(4-Bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl esterYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of toluene-4-sulfonic acid 2-[2-(4-bromophenyl)-5-methyloxazol-4-yl]ethyl ester, 2-(4-hydroxyphenoxy)-2-methylpropanoic acid ethyl ester (American Home Products U.S. Pat. No. 3,795,691) (7.06 g, 31.5 mmol) and Cs2CO3 (13.3 g, 41.0 mmol) was heated at 55° C. in DMF (45 mL) for 18 h. The reaction was partitioned between ethyl acetate (250 mL) and H2O (250 mL), and the aqueous phase extracted with ethyl acetate (2×100 mL). The combined organic phases were dried (MgSO4) and concentrated under reduced pressure to an oil which was purified by column chromatography (1500 mL SiO2, hexanes to 10% ethyl acetate/hexanes) to provide 2-(4-{2-[2-(4-bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methyl propionic acid ethyl ester (6.81 g, 44%) as a off-white solid: Rf=0.48 in 35% ethyl acetate/hexanes; mp 78-79° C.; 1H NMR (300 MHz, CDCl3) δ7.85-7.82 (m, 2H), 7.57-7.53 (m, 2H), 6.83-6.75 (m, 4H), 4.22 (q, J=7.0 Hz, 2H), 4.18 (t, J=6.6 Hz, 2H), 2.94 (t, J=6.7 Hz, 2H), 2.36 (s, 3H), 1.52 (s, 6H), 1.27 (t, J=7.0 Hz, 3H) and by-product 2-(4-Bromophenyl)-5-methyl-4-vinyloxazole (1.81 g, 22%) as a white solid: 1H NMR (300 MHz, CDCl3) δ7.92-7.87 (m, 2H), 7.58-7.55 (m, 2H), 6.54 (dd, J=17.3, 10.8 Hz, 1H), 5.94 (dd, J=17.0, 1.8 Hz, 1H), 5.30 (dd, J=10.8, 1.8 Hz, 1H), 2.41 (s, 3H).

Workup

  1. customThe reaction was partitioned between ethyl acetate (250 mL) and H2O (250 mL)
  2. extractionthe aqueous phase extracted with ethyl acetate (2×100 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 (1500 mL SiO2, hexanes to 10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ac0e22e9f1eb4d50ad2f8698613caed0
Source dataset
uspto-grants-2002_07
Patent number
US06417212B1

Reaction notes

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