Cesium carbonate → 2-(4-{2-[2-(3-Bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester

HRID 2228983Notes

Reaction equation

HRID 2228983 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([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:5]=[CH:6][CH:7]=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:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=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 20823121Toluene-4-sulfonic acid 2-[2-(3-bromophenyl)-5-methyloxazol-4-yl]ethyl ester

Product 1

HCID 120832362-(4-{2-[2-(3-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-(3-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-(3-bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methyl propionic acid ethyl ester (6.81 g, 44%) as a off-white solid. Rf=0.39 in 1:4 ethyl acetate:hexanes; 1H NMR (400 MHz, CDCl3) δ8.11 (t, J=1.6 Hz, 1H), 7.89-7.86 (m, 1H), 7.49 (ddd, J=8.0, 2.0, 1.2 Hz, 1H), 7.27 (t, J=8.0 Hz, 1H), 6.80-6.72 (m, 4H), 4.20 (q, J=7.2 Hz, 2H), 4.15 (t, J=6.6 Hz, 2H), 2.92 (t, J=6.6 Hz, 2H), 2.34 (s, 3H), 1.49 (s, 6H), 1.24 (t, J=7.2 Hz, 3H); MS (EI) 510.1 (M+Na)+, 488.1 (M+H)+.

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-5306da3806904645bc9d14aef00c7b45
Source dataset
uspto-grants-2002_07
Patent number
US06417212B1

Reaction notes

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