Synthesis of Quinine

Structure of Quinine

C20H24N2O2

Principal investigatorEric N. Jacobsen
Publication year2004
Synthesis typeTotal
Number of steps 18 (linear)
References
Part 1 of 1
intermediate structure + intermediate structure
n-BuLi
THF
-78 to 0 °C, 2 h, 84%
intermediate structure
Methyl Cyanoacetate
Cyclohexane, t-BuOH
RT, 48 h, 91%
intermediate structure
H2, Ni (Raney)
MeOH
80 °C, 14 h, 89%
intermediate structure
H2O, i-Pr2NLi
THF
-78 °C to RT, 50 min
intermediate structure
LiAlH4
THF
0 to 35 °C, 11 h
intermediate structure
(BnOCO)2O, Et3N
CH2Cl2
0 °C to RT, 4 h, 51% (3 steps)
"Also isolated was the C3-epimer (19 % yield)."
intermediate structure
NMO, n-Pr4N+ RuO4-
CH2Cl2
RT, 60 min
intermediate structure
KOt-Bu, Ph3P+CH3 Br-
THF
0 °C to RT, 13 h, 73% (2 steps)
See the Wittig Reaction
intermediate structure
n-Bu4N+ F-
THF
0 °C, 4 h
intermediate structure
NMO, n-Pr4N+ RuO4-
CH2Cl2
RT, 60 min, 86% 2 steps)
intermediate structure + intermediate structure
CrCl2
THF
RT, 12 h, 79%
See the Takai Reaction
intermediate structure + intermediate structure
K3PO4, Pd(OAc)2
THF
RT, 16 h, 89%
See the Suzuki Coupling
intermediate structure
AD-mix B, MsNH2
t-BuOH
0 °C, 12 h, 88%
intermediate structure
MeC(OMe)3, Pyr.TsOH
CH2Cl2
RT, 12 h
intermediate structure
AcBr
CH2Cl2
0 °C to RT, 6 h
intermediate structure intermediate structure
K2CO3
MeOH
RT, 2 h, 81% (3 steps)
intermediate structure
Et2AlCl, PhSMe
CH2Cl2
0 °C to RT, 8 h
intermediate structure
MeCN
185 °C, 20 min, 68% (2 steps)
intermediate structure