Synthesis of Morphine

Structure of Morphine

C17H19NO3

Principal investigatorJohann Mulzer
Publication year1996
Synthesis typeFormal
Number of steps 14 (linear)
References
Part 1 of 1
intermediate structure
HCO2Me, NaOMe
PhH
95%
intermediate structure + intermediate structure
Et3N
MeOH
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. TMSCl
  3. Et3N
THF
-78 °C to RT
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. H2O2
  3. NaOH
  4. H2O
THF
70%
intermediate structure
Ni (Raney), KOH
MeOH
98%
intermediate structure
PhSO2NHMe, n-Bu3P
81%
intermediate structure
NBS, Bz2O2
CCl4
Reflux, , 65%
intermediate structure
Li, NH3
THF, t-BuOH
79%
intermediate structure
HCl
H2O
90 °C, , 95%
intermediate structure
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