Cesium carbonate → (S)-2-(4-{2-[5-Methyl-2-(5-methyl-thiophen-2-yl)-oxazol-4-yl]-ethoxy}-benzyl)-2-phenoxy-butyric Acid Ethyl Ester

HRID 1393476Notes

Reaction equation

HRID 1393476 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[C@@:5]([CH3:21])([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)[CH3:2].[CH3:23][C:24]1[O:28][C:27]([C:29]2[S:30][C:31]([CH3:34])=[CH:32][CH:33]=2)=[N:26][C:25]=1[CH2:35][CH2:36]OS(C1C=CC(C)=CC=1)(=O)=O.[C:48]([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:22])[C@:5]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:36][CH2:35][C:25]2[N:26]=[C:27]([C:29]3[S:30][C:31]([CH3:34])=[CH:32][CH:33]=3)[O:28][C:24]=2[CH3:23])=[CH:9][CH:8]=1)([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:21][CH3:48])[CH3:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 60024296(S)-3-(4-hydroxyphenyl)-2-methyl-2-phenoxypropionic acid ethyl esterHCID 86592426Toluene-4-sulfonic acid 2-[5-methyl-2-(5-methyl-thiophen-2-yl)-oxazol-4-yl]ethyl ester

Product 1

HCID 69316116(S)-2-(4-{2-[5-Methyl-2-(5-methyl-thiophen-2-yl)-oxazol-4-yl]-ethoxy}-benzyl)-2-phenoxy-butyric Acid Ethyl EsterYield 47%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

(S)-3-(4-Hydroxyphenyl)-2-methyl-2-phenoxypropionic acid ethyl ester (255 mg, 0.85 mmol), toluene-4-sulfonic acid 2-[5-methyl-2-(5-methyl-thiophen-2-yl)-oxazol-4-yl]-ethyl ester (383 mg, 1.02 mmol) and Cs2CO3 (335 mg, 1.02 mmol) are combined in anhydrous DMF (6 mL) and stirred for 16 h at 55° C. under an atmosphere of nitrogen. The mixture was then cooled and diluted with ethyl acetate (50 mL), and washed with water then brine. The organic layer was dried with MgSO4 and concentrated in vacuo to a viscous tan oil. The residue was purified by flash column chromatography (200 g silica, hexanes to 25% EtOAc/hexanes) to provide the title compound as a colorless oil (201 mg, 47%). 1H NMR (400 MHz, CDCl3) δ 7.39 (d, J=3.4 Hz, 1H), 7.22-7.13 (m, 4H), 6.97 (t, J=7.2 Hz, 1H), 6.85-6.80 (m, 4H), 6.72 (dd, J=3.6, 1.2 Hz, 1H), 4.23-4.17 (m, 4H), 3.26 (A of Abq, J=13.6 Hz, 1H), 3.11 (B of Abq, J=13.6 Hz, 1H), 2.94 (t, J=5.6 Hz, 2H), 2.50 (s, 3H), 2.34 (s, 3H), 1.39 (s, 3H), 1.22 (t, J=7.2 Hz, 3H); MS (EI+) 505.9 (M+H); 637.8 (M+H+Cs).

Workup

  1. temperatureThe mixture was then cooled
  2. washwashed with water
  3. dry with materialThe organic layer was dried with MgSO4
  4. concentrationconcentrated in vacuo to a viscous tan oil
  5. customThe residue was purified by flash column chromatography (200 g silica, hexanes to 25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-81557bef454146b7888dcabeda60f51a
Source dataset
uspto-grants-2008_03
Patent number
US07345070B2

Reaction notes

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