Dimethylformamide → 3-[4-[2-(2-Biphenyl-4-yl-5-methyloxazol-4-yl)ethoxy]-2-(4-trifluoromethylphenoxy-methyl)-phenyl]-propionic acid

HRID 1181127Notes

Reaction equation

HRID 1181127 reaction equation
C(OC(=O)C[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=1)(C)(C)C.[C:29]1([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[CH:34]=[CH:33][C:32]([C:35]2[O:36][C:37]([CH3:53])=[C:38]([CH2:40][CH2:41]OS(C3C=CC(C)=CC=3)(=O)=O)[N:39]=2)=[CH:31][CH:30]=1.[CH3:60]N(C=O)C.[C:65](=[O:68])([O-])[O-:66].[Cs+].[Cs+]>CCOCC>[C:29]1([C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH:34]=[CH:33][C:32]([C:35]2[O:36][C:37]([CH3:53])=[C:38]([CH2:40][CH2:41][O:15][C:12]3[CH:13]=[CH:14][C:9]([CH2:8][CH2:60][C:65]([OH:66])=[O:68])=[C:10]([CH2:16][O:17][C:18]4[CH:23]=[CH:22][C:21]([C:24]([F:25])([F:27])[F:26])=[CH:20][CH:19]=4)[CH:11]=3)[N:39]=2)=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 12966835Toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-methyl-oxazol-4-yl)ethyl esterHCID 589790123-[4-Hydroxy-2-(4-trifluoromethylphenoxymethyl)phenyl]propionic acid tert-butyl ester

Product 1

HCID 102822133-[4-[2-(2-Biphenyl-4-yl-5-methyloxazol-4-yl)ethoxy]-2-(4-trifluoromethylphenoxy-methyl)-phenyl]-propionic acidYield 71%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

General procedure for parallel synthesis using, the DynaVac Carousel apparatus: A 50 mL glass tube with screw cap and nitrogen inlet was charged with 3-[4-hydroxy-2-(4-trifluoromethylphenoxymethyl)phenyl]propionic acid tert-butyl ester (0.050 g, 0.146 mmol), toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-5-methyloxazol-4-yl)ethyl ester (0.078 g, 0.18 mmol), anhydrous DMF (0.5 mL), and then cesium carbonate (0.072 g, 0.22 mmol). The mixture was stirred at ambient temperature for 16 h. MS analysis of the reaction indicated formation of the ester intermediate MS (ES) m/e 658 (M+1). The reaction mixture was poured into ether (30 mL). The organic layer was washed with brine (2×), dried (Na2SO4), and concentrated. The crude residue was diluted with CH2Cl2 (2 mL) and then trifluoroacetic acid (1 mL). The mixture was stirred at ambient temperature for 2 h and concentrated under a stream of N2. The crude product was purified by mass-directed reverse phase HPLC to provide the title compound (0.053 g, 71%). 1H NMR (250 MHz, CDCl3) 2.41 (s, 3H), 2.70 (t, J=7.7 Hz, 2H), 2.95-3.05 (m, 4H), 4.28 (t, J=6.6 Hz, 2H), 5.09 (s, 2H), 6.90 (dd, J=8.5, 2.8 Hz, 1H), 7.01 (d, J=2.6 Hz, 1H), 7.06 (d, J=8.6 Hz, 2H), 7.21 (d, J=8.5 Hz, 1H), 7.41-7.72 (m, 9H), 8.07 (d, J=8.4 Hz, 2H). MS (ES) m/e 602 (M+1).

Workup

  1. customGeneral procedure for parallel synthesis
  2. customthe DynaVac Carousel apparatus: A 50 mL glass tube with screw cap
  3. washThe organic layer was washed with brine (2×)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. additionThe crude residue was diluted with CH2Cl2 (2 mL)
  7. stirringThe mixture was stirred at ambient temperature for 2 h
  8. concentrationconcentrated under a stream of N2
  9. customThe crude product was purified by mass-directed reverse phase HPLC

Sources & evidence

ORD record
ord-591f638edf294b809daaa6080272aee0
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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