Hexane → Tert-butyl {3-[3-(methoxymethoxy)phenyl]-3-oxopropyl}carbamate

Temperature

-78 °C

1-Bromo-3-(methoxymethoxy)benzene (3.938 g, 18.14 mmol) prepared from 3-bromophenol by the method described in Shin-Jikken-Kagaku-Koza (New Experiment Chemistry Lecture) Vol. 14, p. 568 (Maruzen, 1978) was dissolved in tetrahydrofuran (8 mL), and to the solution was gradually added a 1.56 mol/L solution of n-butyl lithium in hexane (12.2 mL, 19.0 mmol) under cooling at −78° C. Subsequently, to the mixture was added THF (16 mL), and then the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was gradually added to tert-butyl[2-(N-methoxy-N-methylcarbamoyl)ethyl]carbamate (this compound is prepared by condensation of N-tert-butoxycarbonyl-β-alanine and N,O-dimethylhydroxylamine hydrochloride) (2.010 g, 8.653 mmol) dissolved in THF (10 mL) at −18° C. The mixture was stirred at the same temperature for 1 hour, then to the mixture was added water and saturated aqueous ammonium chloride, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=1/4) to give tert-butyl{3-[3-(methoxymethoxy)phenyl]-3-oxopropyl}carbamate (1.568 g, 59%).

1. stirringThe mixture was stirred at the same temperature for 1 hour
2. extractionthe mixture was extracted with ethyl acetate
3. washThe organic layer was washed with saturated aqueous sodium chloride
4. dry with materialdried over anhydrous sodium sulfate
5. customthe solvent was evaporated under reduced pressure
6. customThe residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=1/4)

ORD record

ord-a5dffb8a3b2d4e1da0c696d4d70b0192

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318782B2