M-Cresol → 2-Methyl-2-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-2-m-tolyloxymethyl-phenoxy}-propionic acid

HRID 1181142Notes

Reaction equation

HRID 1181142 reaction equation
C(OC(=O)C(OC1C=CC(OCCC2N=C(C3C=CC=CC=3)OC=2C)=CC=1CBr)(C)C)C.C1C(O)=CC=CC=1C.C(=O)([O-])[O-].[K+].[K+].C([O:49][C:50](=[O:85])[C:51]([CH3:84])([O:53][C:54]1[CH:59]=[CH:58][C:57]([O:60][CH2:61][CH2:62][C:63]2[N:64]=[C:65]([C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=3)[O:66][C:67]=2[CH3:68])=[CH:56][C:55]=1[CH2:75][O:76][C:77]1[CH:78]=[C:79]([CH3:83])[CH:80]=[CH:81][CH:82]=1)[CH3:52])C.[OH-].[Na+]>C(O)C>[CH3:84][C:51]([O:53][C:54]1[CH:59]=[CH:58][C:57]([O:60][CH2:61][CH2:62][C:63]2[N:64]=[C:65]([C:69]3[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=3)[O:66][C:67]=2[CH3:68])=[CH:56][C:55]=1[CH2:75][O:76][C:77]1[CH:78]=[C:79]([CH3:83])[CH:80]=[CH:81][CH:82]=1)([CH3:52])[C:50]([OH:85])=[O:49]

Participants

7

Reactant 5

HCID 342M-CresolHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 235900072-{2-Bromomethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methylpropionic acid ethyl esterHCID 692322812-Methyl-2-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]-2-m-tolyloxymethylphenoxy}propionic acid ethyl ester

Product 1

HCID 101640202-Methyl-2-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-2-m-tolyloxymethyl-phenoxy}-propionic acidYield 38%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

General procedure for the parallel synthesis of analogs using the DynaVac Carousel apparatus: A 50 mL glass tube with screw cap and nitrogen inlet was charged with 2-{2-bromomethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methyl-propionic acid ethyl ester (0.040 g, 0.080 mmol), m-cresol (0.012 mL, 0.12 mmol), absolute ethanol (1 mL), and then potassium carbonate (0.022 g, 0.16 mmol; 325 mesh). The mixture was heated to 80° C. for 4 h. MS analysis of the reaction indicated that 2-methyl-2-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]-2-m-tolyloxymethylphenoxy}-propionic acid ethyl ester: MS (ES) m/e 530 (M+1) had formed. The reaction mixture was treated with 2N NaOH (0.4 mL), heated at 55° C. for 3 h, cooled, and concentrated. The residue was treated with 5N HCl (0.75 mL) and CH2Cl2 (1 mL) and was poured onto a 3-mL ChemElute cartridge to remove the aqueous layer. The cartridge was washed with CH2Cl2, and the solvent was removed in vacuo. The crude residue was purified by mass-directed reverse phase HPLC to provide the title compound (0.032 g, 38%). MS (ES) m/e 502 (M+1).

Workup

  1. customGeneral procedure for the parallel synthesis of analogs
  2. customA 50 mL glass tube with screw cap
  3. customMS (ES) m/e 530 (M+1) had formed
  4. temperatureheated at 55° C. for 3 h
  5. temperaturecooled
  6. concentrationconcentrated
  7. additionThe residue was treated with 5N HCl (0.75 mL) and CH2Cl2 (1 mL)
  8. additionwas poured onto a 3-mL ChemElute cartridge
  9. customto remove the aqueous layer
  10. washThe cartridge was washed with CH2Cl2
  11. customthe solvent was removed in vacuo
  12. customThe crude residue was purified by mass-directed reverse phase HPLC

Sources & evidence

ORD record
ord-cc890aca89db4ab68fcb41f73528c17c
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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