Potassium Carbonate → HCID 10209675, compound

HRID 348312Notes

Reaction equation

HRID 348312 reaction equation
C([O:3][C:4](=[O:23])[C:5]([O:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=1)([CH3:14])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)C.[CH3:24][C:25]1[O:29][C:28]([C:30]2[CH:35]=[CH:34][C:33]([C:36]3[S:37][CH:38]=[CH:39][CH:40]=3)=[CH:32][CH:31]=2)=[N:27][C:26]=1[CH2:41][CH2:42]OS(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>C(O)C>[F:22][C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][CH:19]=1)[O:15][C:5]([CH3:14])([CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:42][CH2:41][C:26]2[N:27]=[C:28]([C:30]3[CH:35]=[CH:34][C:33]([C:36]4[S:37][CH:38]=[CH:39][CH:40]=4)=[CH:32][CH:31]=3)[O:29][C:25]=2[CH3:24])=[CH:11][CH:12]=1)[C:4]([OH:3])=[O:23]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 693158132-(3-Fluorophenoxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl esterHCID 86593515HCID 86593515, compound

Product 1

HCID 10209675HCID 10209675, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 2-(3-fluoro-phenoxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl ester (0.030 mmol), toluene-4-sulfonic acid 2-(5-methyl-2-(4-thiophen-2-yl-phenyl)-oxazol-4-yl)ethyl ester (0.030 mmol) (see Ex. 3, Part B) and 325 mesh K2CO3 (0.084 g, 0.60 mmol) in ethanol (2 mL) was heated to reflux for 24 h under N2. Aqueous 5N NaOH (0.5 mL) and additional ethanol (1 mL) was added to the reaction mixture and it was heated at reflux for an additional 2 h. The reaction was cooled and the solvent removed in vacuo. The residue was acidified with aqueous 1 N HCl (5 mL), extracted with water and CH2Cl2 and the organic layer dried by passing it through a Varian Chem Elut 1003 cartridge. The solvent was removed in vacuo to give 2-(3-fluoro-phenoxy)-2-methyl-3-(4-{2-[5-methyl-2-(4-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-phenyl)-propionic acid. 1H NMR (400 MHz, CDCl3) δ 7.99 (d, 2H, J=8.6 Hz), 7.70 (d, 2H, J=8.6 Hz), 7.42 (dd, 1H, J=3.5 Hz, 1.17 Hz), 7.36 (dd, 1H, J=5.1 Hz, 1.17 Hz), 7.18–7.10 (m, 4H), 6.82 (d, 2H, J=8.6 Hz), 6.76–6.60 (m, 3H), 4.21 (t, 2H, J=6.3 Hz), 3.26 (d, 1H, J=14.1 Hz), 3.12 (d, 1H, J=14.1 Hz), 3.07 (t, 2H, J=6.3 Hz), 2.73 (s, 3H), 1.45 (s, 3H). HRMS (ES+) m/z exact mass calcd for C32H28FNO5S 558.1750, found 558.1743.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 24 h under N2
  3. temperaturewas heated
  4. temperatureat reflux for an additional 2 h
  5. temperatureThe reaction was cooled
  6. customthe solvent removed in vacuo
  7. extractionextracted with water and CH2Cl2
  8. customthe organic layer dried
  9. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-710d6dd6790c48989e48af03e837757f
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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