Methanol → 2-{3-[2-(4-Fluorophenyl)oxazol-4-ylmethoxy]phenoxymethyl}-6-methylbenzoic acid

HRID 731130Notes

Reaction equation

HRID 731130 reaction equation
C[O-].[Na+].CO.[OH:6][C:7]1[CH:8]=[C:9]([CH:22]=[CH:23][CH:24]=1)[O:10][CH2:11][C:12]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[C:13]=1[C:14]([OH:16])=[O:15].Cl[CH2:26][C:27]1[N:28]=[C:29]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)[O:30][CH:31]=1.[Cl-].[Na+]>CN1CCCC1=O>[F:38][C:35]1[CH:34]=[CH:33][C:32]([C:29]2[O:30][CH:31]=[C:27]([CH2:26][O:6][C:7]3[CH:8]=[C:9]([CH:22]=[CH:23][CH:24]=3)[O:10][CH2:11][C:12]3[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[C:13]=3[C:14]([OH:16])=[O:15])[N:28]=2)=[CH:37][CH:36]=1

Participants

7

Reactant 5

HCID 887MethanolHCID 5234Sodium ChlorideHCID 10942334Sodium MethoxideHCID 114253992-(3-Hydroxyphenoxymethyl)-6-methylbenzoic AcidHCID 160382604-(Chloromethyl)-2-(4-fluorophenyl)-1,3-oxazole

Product 1

HCID 114078472-{3-[2-(4-Fluorophenyl)oxazol-4-ylmethoxy]phenoxymethyl}-6-methylbenzoic acidYield 58.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

18.6 g of 30% strength solution of sodium methoxide in methanol (104 mmol) are added to 15.9 g (51.6 mmol) of 2-(3-hydroxyphenoxymethyl)-6-methyl-benzoic acid (hemisolvate with N-methylpyrrolidone) in 70 ml of N-methylpyrrolidone while stirring at room temperature. After five minutes, 10.0 g (47.3 mmol) of 4-chloromethyl-2-(4-fluorophenyl)oxazole are added, and the mixture is stirred at room temperature for 23 h and finally heated at 50° C. for one hour. 500 ml of 19% strength sodium chloride solution are added to the reaction solution, and the resulting mixture is extracted twice with 225 ml of ethyl acetate. The combined ethyl acetate phases are extracted three times with 225 ml of water, and the combined aqueous phases are acidified to pH=3 with 2 M hydrochloric acid. The resulting crystals are filtered off with suction and washed with water. The product is purified further by crystallization from isopropanol. 2-{3-[2-(4-Fluorophenyl)oxazol-4-ylmethoxy]phenoxymethyl}-6-methylbenzoic acid is obtained as colorless crystals in a yield of 58.3%, melting point 168-173° C.

Workup

  1. stirringthe mixture is stirred at room temperature for 23 h
  2. temperaturefinally heated at 50° C. for one hour
  3. extractionthe resulting mixture is extracted twice with 225 ml of ethyl acetate
  4. extractionThe combined ethyl acetate phases are extracted three times with 225 ml of water
  5. filtrationThe resulting crystals are filtered off with suction
  6. washwashed with water
  7. customThe product is purified further by crystallization from isopropanol

Sources & evidence

ORD record
ord-a2e4f7410d1d4a6bacd456cc4bd70674
Source dataset
uspto-grants-2009_09
Patent number
US07582794B2

Reaction notes

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