Chloromethyl Methyl Ether → 1-(Dimethoxymethyl)-2-(methoxymethoxy)-3-(trifluoromethyl)benzene

Temperatur

50 °C

After trimethyl orthoformate (130 ml, 1.19 mol) and camphorsulfonic acid (1.55 g, 6.67 mmol) were added to a solution of 2-hydroxy-3-(trifluoromethyl)benzaldehyde (31.7 g, 167 mmol) obtained in Example (6-3) in methanol (50 ml), the mixture was stirred at 50° C. for 6 hours. After the reaction mixture was poured into a 1% aqueous sodium hydrogencarbonate solution and the mixture was extracted with ethyl acetate (three times), the organic layer was successively washed with water (twice) and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by concentrating the organic layer was dissolved in methylene chloride (400 ml) and diisopropylethylamine (50.9 ml, 292 mmol) and chloromethyl methyl ether (15.4 ml, 203 mmol) were successively added thereto under ice-cooling, and the mixture was stirred overnight. After the reaction mixture was poured into water and the mixture was extracted with ethyl acetate (twice), the organic layer was successively washed with 0.5N hydrochloric acid, a 5% aqueous sodium hydrogencarbonate solution, water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=14/1-10/1) to give 1-(dimethoxymethyl)-2-(methoxymethoxy)-3-(trifluoromethyl)benzene as a pale yellow oil (42.2 g, yield: 93%).

1. extractionthe mixture was extracted with ethyl acetate (three times)
2. washthe organic layer was successively washed with water (twice) and a saturated aqueous NaCl solution
3. dry with materialdried with anhydrous sodium sulfate
4. customThe residue obtained
5. concentrationby concentrating the organic layer
6. dissolutionwas dissolved in methylene chloride (400 ml)
7. temperatureunder ice-cooling
8. stirringthe mixture was stirred overnight
9. extractionthe mixture was extracted with ethyl acetate (twice), the organic layer
10. washwas successively washed with 0.5N hydrochloric acid
11. dry with materiala 5% aqueous sodium hydrogencarbonate solution, water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate
12. customThe residue obtained
13. customby removing the solvent under reduced pressure
14. customwas purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=14/1-10/1)

ORD-Eintrag

ord-467f64665b24400d8ef8aa0bfa84e801

Quelldatensatz

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07923573B2