Methods of Non-a-Amino Acid Synthesis, 2nd Edition

80

Methods of Non-α-Amino Acid Synthesis, Second Edition

obviously a conjugate addition reaction (see Chapter 3, Section 3.2), but it is included

here because of the Knoevenagel type process.

23

AcHN

CO

2

Et

CO

2

Et

C

CO

2

Et

CO

2

Et

CO

2

Et

NHAc

EtO

2

C

CO

2

H

NH

2

HO

2

C

+

20% HCl

50°C

30 31 32

94%

67%

NaOEt

EtOH

Doebner condensation

24

with malonic acid itself sometimes leads to very poor

yields of product, as seen above. One reported method that improved the reaction

used nitro-ester 33 rather than malonic acid in a reaction with an ortho-ester and

aniline, and 34 was produced in good yield.

25

In this variation, the amine surrogate

was the nitro group (see Chapter 1, Section 1 ...