Synthesis of Morphine

Structure of Morphine

C17H19NO3

Principal investigatorKenner C. Rice
Publication year1980
Synthesis typeTotal
Number of steps 18 (linear)
References
Part 1 of 1
intermediate structure + intermediate structure
200 °C, 2 h, 95%
intermediate structure
POCl3
MeCN
Reflux, 70 min
intermediate structure
NaBH3CN
H2O, MeOH
Reflux, 90 min, 86% (2 steps)
intermediate structure
Li
NH3, t-BuOH, THF
-75 to -55 °C, 5.5 h, 90%
See the Birch Reduction
intermediate structure
HCO2Ph
EtOAc
Reflux, 45 min, 94%
intermediate structure
(CH2OH)2, MsOH
THF
RT, 60 min
intermediate structure
N-Bromoacetamide
THF
0-5 °C, 30 min
intermediate structure
HCO2H
H2O
RT, 60 min, 90% (3 steps)
intermediate structure
HF, TfOH, NH4F
H2O
0 °C, 72-96 h, 60%
intermediate structure
HCl
H2O, MeOH
Reflux, 18 h, 98%
intermediate structure
Br2
AcOH
RT, 2 h
intermediate structure
NaOH
CHCl3, H2O
0 °C
intermediate structure
CH2O, H2, NaOAc, Pd/C
AcOH, H2O
79% (3 steps)
intermediate structure
ClCO2Me
PhH
Reflux, 16 h, 100%
intermediate structure
HCl, PhSeCl
EtOAc, H2O
RT, 4.5 h, 85%
intermediate structure
NaIO4
EtOAc, H2O
RT, 20 h, 68%
intermediate structure
LiAlH4
THF
Reflux, , 71%
intermediate structure
BBr3
CHCl3
RT, 17 min, 91%
intermediate structure