Synthesis of Morphine

Structure of Morphine

C17H19NO3

Principal investigatorJames D. White
Publication year1999
Synthesis typeFormal
Number of steps 28 (linear)
References
Part 1 of 1
intermediate structure + intermediate structure
NaOMe
MeOH
Reflux, 6 h, 68%
intermediate structure
H2, [RhCl(COD)]2
THF, MeOH
RT, 10 h, 100%
intermediate structure
Br2
AcOH
RT, 10 min, 92%
intermediate structure
P2O5
MsOH
RT, 10 h, 75%
intermediate structure
H2, Pd(OH)2, NaHCO3
MeOH
RT, 45 min, 99%
intermediate structure
LiOH
THF, H2O
RT, 12 h, 100%
intermediate structure
KH, HCO2Me
THF
RT, 8 h
intermediate structure + intermediate structure
Et3N
CH2Cl2
RT, 12 h
intermediate structure
NaOH
THF, H2O
RT, 10 h, 70% (3 steps)
intermediate structure
CH2N2
EtOAc, Et2O
RT, , 90%
intermediate structure
Br2, NaHCO3
CHCl3
0 °C, 90 min, 70%
intermediate structure
DBU
PhH
68 °C, 4 h, 90%
intermediate structure
NaBH4
CH2Cl2, i-PrOH
RT, 12 h, 99%
intermediate structure
H2, Pd/C, NaHCO3
MeOH
RT, 24 h, 75%
intermediate structure
CH2(OMe)2, P2O5
CHCl3
RT, 4 h, 86%
intermediate structure
LiOH
THF, H2O
RT, 20 h, 100%
intermediate structure
(COCl)2, CH2N2
PhH, Et2O
RT, 19 h, 63%
intermediate structure
Rh2(CH3CONH)4
CH2Cl2
RT, 60 min, 65%
intermediate structure
NH2OH.HCl, NaOAc
MeOH
RT, 6 h, 90%
intermediate structure
BsCl, Et3N, DMAP
CH2Cl2
RT, 60 min
intermediate structure
AcOH
RT, 60 min, 69% (2 steps)
intermediate structure
NaH, MeI
PhH
Reflux, 5 h, 95%
intermediate structure
HBr
MeCN, H2O
RT, 2 h, 95%
intermediate structure
Dess-Martin Periodinane
CHCl3
RT, 60 min, 96%
intermediate structure
KOt-Bu, PhSeCl
THF, t-BuOH
0 °C to RT, 90 min
intermediate structure
NaIO4
THF, H2O
RT, 30 h, 64% (2 steps)
intermediate structure
LiAlH4
THF
Reflux, 6 h, 70%
intermediate structure
Remaining...
91% (1 step)
"See : J. Med. Chem. 1977, 20, 164."
intermediate structure