Synthesis of Morphine

Structure of Morphine

C17H19NO3

Principal investigatorJohann Mulzer
Publication year1996
Synthesis typeFormal
Number of steps 14 (linear)
References
Angew. Chem. Int. Ed. 1996, 35, 2830.
Part 1 of 1
intermediate structure
NaOMe, HCO2Me
PhH
95%
See the Claisen Condensation
intermediate structure + intermediate structure
Et3N
MeOH
See the Robinson Annulation
intermediate structure
KOH
Dioxane , H2O
77% (2 steps)
"The enantiomers were resolved on a preparative scale by chromatography on cellulose triacetate."
intermediate structure
  1. Vinyl2CuMgCl
  2. Et3N , TMSCl
THF
-78 °C to RT
See the Michael Addition
intermediate structure
NBS
THF
-78 °C, 63% (2 steps)
"Also isolated was the CX-epimer (21 % yield)."
intermediate structure
DMF
140 °C, 100%
intermediate structure
TMSCl, (CH2OH)2
CH2Cl2
92%
intermediate structure
  1. BH3.Me2S
  2. H2O , NaOH , H2O2
THF
70%
intermediate structure
KOH, Ni (Raney)
MeOH
98%
intermediate structure
Special reagent
n-Bu3P, PhSO2NHMe
81%
See the Mitsunobu Reaction
intermediate structure
Bz2O2, NBS
CCl4
Reflux, 65%
intermediate structure
Li, NH3
t-BuOH, THF
79%
intermediate structure
HCl
H2O
90 °C, 95%
intermediate structure
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Remaining...
39% (7 steps)
"See : J. Med, Chem, 1976, 19, 1171; J. Med. Chem. 1977, 20, 164; J. Am. Chem. Soc. 1953, 75, 4340."
intermediate structure