An efficient chiral moderator prepared from inexpensive (+)-3-carene: synthesis of the HIV-1 non-nucleoside reverse transcriptase inhibitor DPC 963.
The beta-amino alcohol 4 beta-morpholinocaran-3 alpha-ol is prepared by addition of morpholine to alpha-3,4-epoxycarane utilizing anhydrous magnesium bromide as Lewis acid promoter. The enantiopure amino alcohol is uniquely effective as a chiral moderator for the addition of lithium cyclopropylacetylide to an unprotected N-acylketimine. This reaction provides an efficient route to the second generation NNRTI drug candidate DPC 963.
Kauffman
G S
GS
DuPont Pharmaceuticals Company, Chemical Process R&D, Chambers Works, PRF Building S1, Deepwater, New Jersey 08023, USA.
Harris
G D
GD
Dorow
R L
RL
Stone
B R
BR
Parsons
R L
RL
Pesti
J A
JA
Magnus
N A
NA
Fortunak
J M
JM
Confalone
P N
PN
Nugent
W A
WA
D015497:HIV-1 / Q000201:enzymology*; D015363:Quinolones / Q000138:chemical synthesis*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis*; D013237:Stereoisomerism
C415683:DPC 963; D015363:Quinolones; D018894:Reverse Transcriptase Inhibitors