تفاعل #358543

معادلة التفاعل

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

المردود 64.0%

المذيبات

methylene chloride

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةwith cooling
2. 2
   workup.STIRRINGThe mixture was stirred 18 hours
3. 3
   غسيلThe 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
   تجفيفdried (sodium sulfate)
5. 5
   ترشيحfiltered
6. 6
   أخرىthe solvent evaporated under reduced pressure
7. 7
   أخرىto give crude product (15.30 g, 71%) as a yellow oil
8. 8
   أخرىThe crude product was purified by flash column chromatography on silica gel
9. 9
   غسيلeluting with a gradient of 50:50 to 75:25 ethyl acetate/hexane

الإجراء التجريبي

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).

المصدر