Synthesis of Morphine

Structure of Morphine

C17H19NO3

Principal investigatorMarshall D. Gates
Publication year1952
Synthesis typeTotal
Number of steps 27 (linear)
References
Part 1 of 1
intermediate structure
BzCl, Pyr
Dioxane
100 °C, 3 h, 71%
intermediate structure
NaNO2
AcOH, H2O
0 °C, 2 h, 89%
intermediate structure
H2, Pd/C
AcOH
RT, 45 min
intermediate structure
HCl, FeCl3
H2O
RT, , 88% (2 steps)
intermediate structure
SO2
H2O, MeOH
RT, 30 min, 91%
intermediate structure
K2CO3, Me2SO4, NaHSO3
Acetone
RT, 3 h, 82-86%
intermediate structure
KOH, NaHSO3
H2O, MeOH
RT, , 80%
intermediate structure
NaNO2
AcOH, H2O
-10 °C, 25 min, 97%
intermediate structure
H2, H2SO4, Pd/C
AcOH
RT, 60 min
intermediate structure
HCl, FeCl3
H2O
RT, , 89% (2 steps)
intermediate structure
Et3N, K3Fe(CN)6, NCCH2CO2Et
EtOH, H2O
RT, 11 min, 84%
intermediate structure
KOH
H2O, MeOH
25-30 °C, 4 min, 97%
intermediate structure
1,3-Butadiene
Dioxane
85-87 °C, 72 h, 66%
intermediate structure
H2, Cu2Cr2O5
EtOH
124-131 °C, 4 h, 50%
intermediate structure
KOH, NH2NH2
Diethylene glycol
155 °C, 60 min, 92%
intermediate structure
MeI, NaH
PhMe
Reflux, 3.5 h
intermediate structure
LiAlH4
Et2O
Reflux, 48 h, 88% (2 steps)
"The enantiomers were resolved with dibenzoyl-(+)-tartaric acid (72 % yield)."
intermediate structure
H2SO4
H2O
100 °C, 5 d, 28%
intermediate structure
KOH, NH2NH2
Diglyme
221-227 °C, 75 min, 33%
"The yield was 54 % brsm."
intermediate structure
KOt-Bu, Ph2CO
PhH, t-BuOH
Reflux, 2.5 h, 90%
intermediate structure
  1. Br2
  2. 2,4-Dinitrophenylhydrazine
AcOH
RT to reflux, 24 h, 41%
intermediate structure
HCl
Acetone, H2O
Reflux, 20 min, 60%
intermediate structure
H2, PtO2
EtOH
RT, , 80%
intermediate structure
  1. Br2
  2. NaOAc
  3. 2,4-Dinitrophenylhydrazine
AcOH
RT, 24 h, 26%
intermediate structure
HCl
Acetone, H2O
Reflux, 20 min, 27%
intermediate structure
LiAlH4
THF
Reflux, 46 h, 37%
intermediate structure
Pyr.HCl
220 °C, 6 min, 34%
intermediate structure