Reacción #358543

Ecuación de reacción

O,N-dimethylhydroxylamine hydrochloride

cis-4-{[(tert-butoxycarbonyl)amino]methyl}-cyclohexanecarboxylic acid

N-methylpiperidine

methyl chloroformate

→

tert-butyl [(cis-4-{[methoxy(methyl)amino]carbonyl}cyclohexyl)methyl]carbamate

Rendimiento 64.0%

Disolventes

methylene chloride

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturawith cooling
2. 2
   workup.STIRRINGThe mixture was stirred 18 hours
3. 3
   LavadoThe mixture was washed with 10% citric acid solution (100 ml), saturated sodium carbonate solution (100 ml), water (100 ml), and brine (100 ml)
4. 4
   Secadodried (sodium sulfate)
5. 5
   Filtraciónfiltered
6. 6
   Otrothe solvent evaporated under reduced pressure
7. 7
   Otroto give crude product (15.30 g, 71%) as a yellow oil
8. 8
   OtroThe crude product was purified by flash column chromatography on silica gel
9. 9
   Lavadoeluting with a gradient of 50:50 to 75:25 ethyl acetate/hexane

Procedimiento

To a solution of cis-4-{[(tert-butoxycarbonyl)amino]methyl}-cyclohexanecarboxylic acid (18.53 g, 72.0 mmol) and N-methylpiperidine (21.9 ml, 17.8 g, 180 mmol) in methylene chloride (360 ml) under nitrogen cooled in an ice-bath was adde dropwise methyl chloroformate (6.13 ml, 7.48 g, 79.2 mmol). The solution was stirred 15 minutes with cooling, and O,N-dimethylhydroxylamine hydrochloride (8.43 g, 86.4 mmol) was added. The mixture was stirred 18 hours while warming from ice-bath temperature to ambient temperature. The mixture was washed with 10% citric acid solution (100 ml), saturated sodium carbonate solution (100 ml), water (100 ml), and brine (100 ml), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure to give crude product (15.30 g, 71%) as a yellow oil. The crude product was purified by flash column chromatography on silica gel, eluting with a gradient of 50:50 to 75:25 ethyl acetate/hexane to give tert-butyl [(cis-4-{[methoxy(methyl)amino]carbonyl}cyclohexyl)methyl]carbamate (13.76 g, 64%) as a pale yellow oil. 1H NMR (CDCl3) 4.61 (1H, br s), 3.68 (3H, s), 3.17 (3H, s), 3.11 (2H, t, J 6.5 Hz), 2.79 (1H, m), 1.75 (3H, m), 1.68-1.52 (6H, m), 1.44 (9H, s).

Fuente