Synthesis of N-(1-Isopropyl-vinyl)-N-(4-methoxy-benzyl)-malonamic acid methyl ester; EnamidesSyntheticPage 181 (2001)
Submitted 17th Dec 2001, published 19th Dec 2001
John P. McDonagh
A contribution from the Clark Group, Warwick
3-methyl-2-butanone,p-methoxybenzylamine, Methyl malonyl chloride, N,N-diethylaniline
A solution of 3-methyl-2-butanone (1.1 ml, 10 mmol) and the p-methoxybenzylamine (1.3 ml, 10 mmol) in toluene (20 ml) was stirred under reflux in a Dean and Stark apparatus until no starting material could be detected by tlc analysis (typically 4 hours). The solution was then cooled to 0°C with stirring. Methyl malonyl chloride (1.1 ml, 10 mmol) was added dropwise to this solution, followed by the slow, dropwise addition of N,N-diethylaniline (1.6 ml, 10 mmol). The reaction was then stirred for 2 hours at room temperature and dropped onto H2O (30 ml). The organic layer was washed with 10% aq.HCl (10 ml), H2O (10 ml) dried over MgSO4 and concentrated in vacuo to give a residue which was purified by column chromatography, petroleum ether : ethyl acetate (1:1)(1.9 g, 63 %).
Slow addition of both the acylating agent and base is important in this procedure for successful N-acylation over competitive C-acylation.
A side product in this reaction has been indentified as 2-Isopropyl-3-(4-methoxy-benzyl)-6-methoxycarbonylmethyl-2-methyl-4-oxo-3,4-dihydro-2H-[1,3]oxazine-5-carboxylic acid methyl ester (~10 %).
The imine intermediate can be isolated and stored if required.
1H NMR (250 MHz, CDCl3) d 7.17 (2H, d, J = 8.8 Hz, CHCHCOCH3), 6.76 (2H, d, J = 8.8 Hz, CH=COCH3), 4.98 (1H, s, CHH=C), 4.64 (1H, s, CHH=C), 4.60 (2H, br s, CH2N), 3.72 (3H, s, OCH3), 3.67 (3H, s, OCH3), 3.44 (2H, s, COCH2CO), 2.39 (1H, sep, J = 6.7 Hz, CH(CH3)2), 1.04 (6H, d, J = 6.7 Hz, CH(CH3)2)
D. T. Davies, N. Kapur, A. F. Parsons, Tetrahedron, 2000, 56, 3941
This page has been viewed approximately 214 times since records began.
Get CDX file (Choose "Open this file from its current location" TWICE)
SyntheticPagesTM are for use
exclusively by those with training and experience in synthetic chemistry. While contributors
are asked to identify hazards and to use methods designed to reduce risk, no formal hazard
or risk assessments are included, and these procedures must be conducted at one's own risk.
SyntheticPages, its editors, owners and associates do not warrant or guarantee the safety of
individuals using these procedures and hereby disclaim any liability for any injuries or damages
claimed to have resulted from or related in any way to the procedures herein. Copyright ©2004 Synthetic Pages
Comment on this page!
Registered users may add comments to other pages. If you have already registered, please
log in, otherwise you may
Back to List