Water → HCID 86675824, compound

Temperature

60 °C

To dimethyl malonate (102 mL), a solution of sodium methoxide in methanol (28%, 90.4 mL) was added at room temperature, and the mixture was stirred at 60° C. for 30 minutes. The white suspension was cooled to room temperature. Then, tert-butyl (3-bromopropyl)carbamate (106 g) was added thereto at once, and the mixture was stirred at room temperature for 12 hours. To the reaction solution, water was added, and organic matter was extracted with diethyl ether. The organic layer was washed with a 1 N aqueous sodium hydroxide and saturated sodium chloride solution in this order, then dried over anhydrous sodium sulfate, and filtered, and the solvent was distilled off under reduced pressure to obtain a crude product of dimethyl {3-[(tert-butoxycarbonyl)amino]propyl}malonate. The obtained ester (94 g) was dissolved in methanol (100 mL). To the solution, a solution of lithium hydroxide monohydrate (13.6 g) in water (300 mL) and methanol (300 mL) was added at 0° C., and the mixture was stirred at room temperature for 15 hours. Methanol was distilled off under reduced pressure, and organic matter was extracted with ethyl acetate. 2 N hydrochloric acid (160 mL) was added to the aqueous layer, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, then dried over anhydrous sodium sulfate, and filtered, and the solvent was distilled off under reduced pressure to obtain a crude product. This crude product was purified by silica gel column chromatography (eluting solvent: methylene chloride-methylene chloride/methanol=10/1) to obtain the title compound (69.1 g).

1. temperatureThe white suspension was cooled to room temperature
2. stirringat once, and the mixture was stirred at room temperature for 12 hours
3. extractionorganic matter was extracted with diethyl ether
4. washThe organic layer was washed with a 1 N aqueous sodium hydroxide and saturated sodium chloride solution in this order
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. distillationthe solvent was distilled off under reduced pressure

ORD record

ord-3be2386b7e3c49b1802b59fb90ca72b2

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609710B2