反应 #358543

反应方程式

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

收率 64.0%

溶剂

methylene chloride

反应条件

后处理

1. 1
   温度with cooling
2. 2
   workup.STIRRINGThe mixture was stirred 18 hours
3. 3
   洗涤The 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
   干燥dried (sodium sulfate)
5. 5
   过滤filtered
6. 6
   其他the solvent evaporated under reduced pressure
7. 7
   其他to give crude product (15.30 g, 71%) as a yellow oil
8. 8
   其他The crude product was purified by flash column chromatography on silica gel
9. 9
   洗涤eluting with a gradient of 50:50 to 75:25 ethyl acetate/hexane

实验过程

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).

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