Synthesis of Reserpine

Structure of Reserpine

C33H40N2O9

Principal investigatorRobert B. Woodward
Publication year1956
Synthesis typeTotal
Number of steps 28 (3 parts)
References
Part 1 of 3
intermediate structure
  1. (CH2O)n
  2. HCl
  3. NaNO2
  4. NaOAc
  5. NH2OH.HCl
  6. CuSO4
H2O
0-5 °C
intermediate structure
NH4FeSO4.12H2O
H2O
40 min, 63% (2 steps)
intermediate structure
MeNO2, NH4OAc
AcOH
Reflux, 2 h, 65%
See the Henry Reaction
intermediate structure
H2, Pd/C
AcOH, EtOAc, EtOH
RT, , 55%
intermediate structure
(COCl)2
Et2O
0 °C, 30 min, 90%
intermediate structure
NH3
H2O
40-50 °C, 30 min, 90%
intermediate structure
LiAlH4
THF
Reflux, ON, 63%
intermediate structure
Part 2 of 3
intermediate structure + intermediate structure
PhH
Reflux, 10 h, 8%
""[This method was not] investigated extensively with a view to determining optimum conditions.""
intermediate structure
Al(Oi-Pr)3
i-PrOH
Reflux, 60 min, 60%
intermediate structure
Br2
MeOH
RT, 45 min, 46%
intermediate structure
NaOMe
MeOH
RT, 2.5 h, 84%
intermediate structure
H2SO4, NBS
H2O
60 to 90 °C, 40 min
intermediate structure
CrO3
AcOH, H2O
RT, 10 h, 60% (2 steps)
See the Jones Oxidation
intermediate structure
Zn
AcOH
17 °C, 2 min, 79%
intermediate structure
CH2N2
Dioxane , Et2O
10 °C, , 96%
intermediate structure
Ac2O
Pyr
80-90 °C, 2 h, 92%
intermediate structure
KClO3, OsO4
CCl4, H2O
RT, 8 h, 46%
intermediate structure
HIO4
H2O
RT, 20 min
intermediate structure
CH2N2
Et2O
0 °C, 3 min
intermediate structure
Part 3 of 3
intermediate structure + intermediate structure
PhH
RT, 3 min
intermediate structure
NaBH4
MeOH
RT to Reflux, 10 min, 81% (4 steps)
intermediate structure
POCl3
Reflux, 2 h
intermediate structure
NaBH4
H2O, MeOH
RT, 5 min, 70%
intermediate structure
KOH
H2O, MeOH
Reflux, 2 h, 100%
intermediate structure
DCC
Pyr
100 °C, 2 h, 67%
intermediate structure
t-BuCO2H
Xylene(s)
Reflux, 16 h, 74%
intermediate structure
NaOMe
MeOH
Reflux, 90 min, 79%
intermediate structure + intermediate structure
Pyr
RT, 4 d, 57%
intermediate structure