Synthesis of Morphine

Structure of Morphine

C17H19NO3

Principal investigatorBarry M. Trost
Publication year2002
Synthesis typeFormal
Number of steps 13 (linear)
References
Part 1 of 1
intermediate structure + intermediate structure
Et3N, (n3-C3H3PdCl)2
CH2Cl2
RT, 8 h, 72%
intermediate structure
HC(OMe)3, TsOH
MeOH
50 °C, 4 h, 100%
intermediate structure
i-Bu2AlH
PhMe
-78 °C, 60 min, 85%
intermediate structure
DIAD, Ph3P
Et2O
-20 °C, 5 h
intermediate structure
TsOH
H2O, THF
RT, 4 h, 84% (2 steps)
"98:02 er after recrystallization."
intermediate structure
Pd(OAc)2, dppp, Ag2CO3
PhMe
107 °C, 24 h, 91%
See the Heck Coupling
intermediate structure
Ph3P, CBr4
CH2Cl2
0 °C, 10 min, 91%
intermediate structure
n-Bu3SnH, Pd(PPh3)4
PhMe
RT, 20 min, 88%
See the Stille Coupling
intermediate structure
Pd(OAc)2, dppp, Ag2CO3
PhMe
107 °C, 4 h, 65%
See the Heck Coupling
"The yield was 74 % brsm."
intermediate structure
Dess-Martin Periodinane, SeO2
Dioxane
75 °C to RT, 4.5 h, 58%
intermediate structure
i-Bu2AlH, NaBH4, MeNH2, NH4Br
CH2Cl2, Et2O
-78 °C to RT, ON, 89%
intermediate structure
i-Pr2NLi
THF
RT, 6 h, 57%
intermediate structure
Remaining...
91% (1 step)
"See : J. Med. Chem. 1977, 20, 164."
intermediate structure