Synthesis of Morphine

C17H19NO3
Principal investigator | Gilbert Stork |
---|---|
Publication year | 2009 |
Synthesis type | Formal |
Number of steps | 22 (linear) |
References |
Part 1 of 1
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TsOH,
HO(CH2)3OH
Dean-Stark
PhMe
Reflux, 85%



HCl
H2O, THF
0 °C, 90 min, 80%


HCl
H2O, THF
RT, 2.5 h, 86%


- AgOTf , Cp2ZrHCl
- Imidazole , TESCl
CH2Cl2
-78 °C to RT, 19.5 h, 95%

Et3N
Decalin
235-240 °C, 24 h, 55%
See the Diels-Alder Reaction
"The yield was 70 % brsm. Also isolated was the C2-epimer (14 % yield)."

LiBHEt3
CH2Cl2
0 °C, 90 min, 86%
"The yield was 90 % brsm."



n-Bu4N+ F-
THF
-50 °C to RT, 2 h, 88%


Li(s-Bu)3BH
THF
-20 °C to RT, 6 h, 53%
"The yield was 70 % brsm."

Et3N,
MsCl
CH2Cl2
0 °C, 6 h, 74%
"The yield was 90 % brsm."

HCl
H2O, THF
0 °C, 5 h, 86%
"The yield was 98 % brsm."

Et3N,
NaBH4,
Ti(Oi-Pr)4,
MeNH2.HCl
MeOH
0 °C to RT, 4 h, 93%

K2CO3
PhH
75 °C, 24 h, 73%

NaHCO3,
ClCO2Me
CHCl3
Reflux, 17 h, 91%

SeO2,
t-BuOOH
H2O
Reflux, 15 h, 72%
"The yield was 89 % brsm."

LiAlH4
Et2O
-30 °C to Reflux, 3.5 h, 82%

Remaining...
91% (1 step)
"See : J. Med. Chem. 1977, 20, 164."
