[3853-06-3] · C6H13NO2 · Methyl 3-(Dimethylamino)propionate · (MW 131.20)
(masked acrylate synthetic equivalent; for preparation of a-methylene esters, acids, and lactones2)
Physical Data: bp 56 °C/15 mmHg.
Solubility: sol all common solvents.
Form Supplied in: colorless liquid.
Analysis of Reagent Purity: 1H and 13C NMR; GC.
Preparative Method: reaction of Methyl Acrylate with dimethylamine in ether at 0-25 °C.3
Purification: distillation at reduced pressure.
Handling, Storage, and Precautions: routine laboratory techniques; exhibits typical tendency of amines to undergo slow oxidation in the air. Use in a fume hood.
Methyl 3-(dimethylamino)propionate undergoes straightforward enolate formation upon treatment with Lithium Diisopropylamide. The resulting enolate undergoes high yield reactions with a number of alkylating agents. A representative reaction sequence is shown using a cyclic allylic halide (eq 1). The alkylation product is converted to the quaternary ammonium salt using Iodomethane followed by 1,5-Diazabicyclo[4.3.0]non-5-ene-induced elimination to give the 2-substituted acrylate derivative. Among the possible further reactions are iodo lactonization of the free acid and then either 1,8-Diazabicyclo[5.4.0]undec-7-ene-induced dehydroiodination or Tri-n-butylstannane-promoted reductive deiodination.
The primary motivation for the development of this reagent and a large number of related methods was the common natural occurrence of a-methylene lactones. Literally thousands of these compounds are known, and several of them possess antitumor activity.1 The other methods are too numerous to describe here,1 but a recent modification of the present method employs imines in place of alkyl halides in the reaction of the enolate; the ultimate products are a-alkylidene-b-lactam derivatives.4
University of Notre Dame, IN, USA