Synthesis of 6-Demethyl-6-deoxytetracycline

Structure of 6-Demethyl-6-deoxytetracycline

C21H22N2O7

Principal investigatorRobert B. Woodward
Publication year1962
Synthesis typeTotal
Number of steps 24 (linear)
References
Part 1 of 1
intermediate structure
  1. NaH
  2. MeOAc
  3. ClCH2CO2Me
DMF
50-60 °C, 4.5 h, 55%
intermediate structure
Methyl acrylate, Me3N+Bn HO-
Dioxane
50-70 °C, 60 min, 88%
intermediate structure
H2SO4
AcOH, H2O
Reflux, 24 h
intermediate structure intermediate structure
H2SO4
MeOH, CHCl3
Reflux, 24 h, 44% (2 steps)
intermediate structure
H2, Pd/C
AcOH
30 °C, 2 h
intermediate structure
H2SO4
MeOH, CHCl3
Reflux, 24 h, 69% (2 steps)
"This step was required for purification purposes (3.3 kg scale!)"
intermediate structure
NaOH
H2O
100 °C, 18 h
intermediate structure
Cl2, I2
AcOH
12-17 °C, 7.5 h
intermediate structure
HF
H2O
15 °C, 18 h, 63% (3 steps)
intermediate structure
H2SO4
MeOH, CHCl3
Reflux, 20 h, 66%
intermediate structure
(CO2Me)2, NaH
DMF, MeOH
35-80 °C, , 44%
intermediate structure
HCl
AcOH, H2O
90-94 °C, 45 min, 73%
intermediate structure + intermediate structure
Mg(OMe)2
PhMe
Reflux, 2.5 h, 52%
intermediate structure
Me2NH
H2O
0 °C, 2 h
intermediate structure
NaBH4
DME, H2O
-78 to °C, 30 min, 53% (2 steps)
intermediate structure
TsOH
PhMe
Reflux, 3 h, 90%
intermediate structure
Zn
HCO2H
RT, 1 min, 81%
intermediate structure
H2, Pd/C
EtOH, Et3N
RT, 3 h, 91%
intermediate structure
ClCO2i-Pr, Et3N
CHCl3
0 °C, 30 min
intermediate structure + intermediate structure
MeCN
RT, ON
intermediate structure
NaH
MeOH, DMF
RT to 155 °C, 20 min
intermediate structure
HBr
H2O
100 °C, 20 min, 9-15% (4 steps)
"Yield BRSM"
intermediate structure
O2, CeCl3.7H2O
DMF, MeOH, Buffer (pH = 10.4)
RT, 15 min
intermediate structure
HCl, CaCl2
n-BuOH, H2O, Ethanolamine
Reflux, 3.5 h, 6% (2 steps)
intermediate structure