Triethylamine → Benzyl 3-[methoxy(methyl)carbamoyl]piperidine-1-carboxylate

A 1000-mL 3-necked round-bottom flask was charged with a solution of N-methoxymethan amine hydrochloride (21.45 g, 217.7 mmol, 1.10 equiv, 99%) in dichloromethane (DCM) (250 mL). To the mixture was added Et3N (22.22 g, 217.80 mmol, 1.10 equiv, 99%) at 0-10° C., followed by addition 1-(benzyloxycarbonyl)piperidine-3-carboxylic acid (58 g, 220.3 mmol, 1.00 equiv) in dichloromethane (150 mL) drop wise at 2° C. over 2 hr period. To this mixture was added EDC.HCl (42.02 g, 217.80 mmol, 1.10 equiv, 99%) in several batches while maintaining the temperature below 5° C. The resulting solution was allowed to stir at room temperature overnight. The progress was monitored by TLC (EtOAc: PE=1:1). Upon completion, the reaction was then quenched by the addition of water (500 mL). The resulting mixture was then extracted with dichloromethane (2×500 mL). Combined organic layers were dried over anhydrous magnesium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by a silica gel column chromatography eluted with ethyl acetate/petroleum ether (1:10) affording benzyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate as a white syrup (57 g, 83%).

1. temperaturewhile maintaining the temperature below 5° C
2. customUpon completion, the reaction was then quenched by the addition of water (500 mL)
3. extractionThe resulting mixture was then extracted with dichloromethane (2×500 mL)
4. dry with materialCombined organic layers were dried over anhydrous magnesium sulfate
5. concentrationconcentrated on a rotary evaporator
6. customThe resulting residue was purified by a silica gel column chromatography
7. washeluted with ethyl acetate/petroleum ether (1:10)

ORD-Eintrag

ord-41c765a8428c4ceabe0866aad197ec16

Quelldatensatz

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08080566B1