Water → HCID 69472042, compound

HRID 854563Notes

Reaction equation

HRID 854563 reaction equation
Cl[CH2:2][C:3]1[O:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[N:5][C:4]=1[CH3:18].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:25]([O:27][C:28](=[O:39])[CH2:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([SH:37])=[CH:33][C:32]=1[CH3:38])[CH3:26].O>C(#N)C>[CH2:25]([O:27][C:28](=[O:39])[CH2:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([S:37][CH2:2][C:3]2[O:7][C:6]([C:8]3[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=3)=[N:5][C:4]=2[CH3:18])=[CH:33][C:32]=1[CH3:38])[CH3:26]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 16641178Ethyl (4-mercapto-2-methylphenoxy)acetateHCID 21300976HCID 21300976, compound

Product 1

HCID 69472042HCID 69472042, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of 5-chloromethyl-4-methyl-2-(4-trifluoromethyl-phenyl)-oxazole (0.30 g, 1.8 mmol) and Cs2CO3 in 8 mL acetonitrile is added (4-Mercapto-2-methyl-phenoxy)-acetic acid ethyl ester (0.25 g, 1.1 mmol). The solution is stirred for 6 hrs and poured into water (50 mL) and extracted with ethyl acetate (3×25 mL). The combined organics are washed with water (10 mL) and brine (30 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude product is purified using flash column chromatography (10%-20% ethyl acetate/hexanes) to afford 0.40 g (79%) of {2-Methyl-4-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-ylmethylsulfanyl]-phenoxy}-acetic acid ethyl ester. To a stirred solution of this ester (0.21 g, 0.44 mmol) is added m-CPBA (50%) (0.31 g, 0.89 mmol) at 0° C. After 10 min. the solution is poured into water (50 mL) and extracted with methylene chloride (3×20 mL). The combine methylene chloride layers are washed with 1 N NaOH (25 mL), water (25 mL) and brine (25 mL), dried (Na2SO4), filtered and concentrated in Vacuo. The crude sulphone is purified using flash column chromatography (10%-25% ethyl acetate hexanes) to give 0.15 g (68%) of {2-Methyl-4-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-ylmethanesulfonyl]-phenoxy}-acetic acid ethyl ester. Hydrolysis of this sulphone (0.15 g, 0.30 mmol) occurred under the usual conditions (3 eq. of a 1N solution of LiOH in 1 mL of a 3:2:1 solution of THF:MeOH:H2O) to provide the title compound 0.11 g (78%) after workup with aq. NH4Cl and ethyl acetate.

Workup

  1. extractionextracted with ethyl acetate (3×25 mL)
  2. washThe combined organics are washed with water (10 mL) and brine (30 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified

Sources & evidence

ORD record
ord-7f835dd0eccb49ec9a31950033544406
Source dataset
uspto-grants-2007_08
Patent number
US07259175B2

Reaction notes

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