by reaction of the thus-formed amine withtert-butyloxycarbonic anhydride
leads to intermediate 170 as a single diastereomers.^25
In a three component synthesis, the amide 171 , obtained from ester 170
and benzyl isocyanide, are reacted with the piperidone ( 172 ). The product
from this transform consists of the addition product ( 173 ), where amide
nitrogen in 170 , as well as that on the isocyanide has added to the carbonyl
group on the piperidine. Treatment of adduct 173 with strong acid hydro-
lyzes the urethane function on thet-BOC protecting group leaving behind
the primary amine ( 174 ). Intermediate 174 is not isolated, but undergoes
displacement of the benzyl amine function in an intramolecular amide
exchange to form the diketo pyridazine ( 175 ). Hydrogenation of 176
removes the benzyl protecting group to reveal the free piperidine ( 177 ).
HO
H 2 N
O
171N+O172BuNH 2
NHONHCO 2 tBu NHCO^2 tBu
OHN
NHO173CF 3 CO 2 HNCH 2 C 6 H (^5) CH 2 C 6 H 5 CH 2 C 6 H 5
CH 2 C 6 H 5
CH 2 C 6 H 5
HO
NH
O
HN
NH
O
C 6 H 5 CH 2
C 6 H 5 CH 2 NC C 6 H 5 CH 2
N
NH
HN O
O
HO
N
NH
HN O
O
HO
H
H 2
NH
NH
HN O
O
HO
O
O=HC CO 2 H
O
CO 2 H
H 2
N
NH
HN O
O
HO
(^176175174)
177
178
179
- COMPOUNDS WITH TWO HETEROATOMS 135