Chemistry Reference
In-Depth Information
O
OH
O
MgCl
Br
P
2
O
5
DMSO, Et
3
N
Me
CO
2
+ H
2
Ph
Ph
Me
Ph
Me
KOBu
t
cat.
Ph
28
25
26
27
O
O
O
N
O
R
3
R
4
NH
O
3
N
OMe
H
2
/Pd
Ph
Me
24
(racemic)
Ph
Me
Ph
Me
31
29
30
In summary, waste minimisation in pharmaceuti-
cal manufacture is most effective if implemented at
the design phase of the process, with a balanced
approach after careful consideration of related issues.
The few principles in the process development can
be summarised by the acronym
SEERS
: Safety,
Ecology (or Environment), Efficiency (or Economy),
Robustness (or Reproducibility) and Speed. Striving
for creative and simple solutions to address all these
concerns is the responsibility for all forward-looking
scientists and engineers.
Scheme 12.13
preventing it from contaminating the downstream
intermediate. For the same reason, any residual
compound
28
in the processing stream of compound
29
resulting from incomplete alkylation would not
have the eventual aldehyde moiety and thus was
unable to participate in the amine formation step.
This controlling mechanism, in combination with
the fact that every step gave >90% yield, makes
the overall process quite efficient. In this particular
case, selection of the appropriate starting material
with the key attributes is critical. Understanding the
commodity and speciality chemical supply chains
also was helpful.
References
1.
Wood McKenzie's PharmaQuant
TM
on-line at
http://www.woodmac.com/pharma.htm.
2.
Anastas, P. T., & Williamson, T. C.
ACS Symp. Ser.
, 1996,
626
, 1.
5 Conclusion
3.
Anastas, P. T., & Williamson, T. C.
Green Chemistry:
Frontiers in Benign Chemical Syntheses and Processes
.
Oxford University Press, Oxford, 1998.
Although much progress has been made by genera-
tions of chemists in the search for reaction efficiency
and selectivity, we are still far from matching
nature's ability at accomplishing sophisticated trans-
formations in water with graceful ease and amazing
accuracy. For example, it is always a sobering
reminder when we compare the E factor differences
in enzymatic and chemical-based peptide coupling
procedures. As we ponder about the sustainability of
a particular process,
balance
—whether in an ecolog-
ical sense or from a mere material inventory per-
spective—is the primary question we have to
answer. To put it simply, whatever we put into a
reactor or a plant we have to get out, either as a
product, with all the promises to improve the quality
of human life, or as waste, which does just the
opposite.
4.
Tundo, P., Anastas, P., Black, D. S., Breen, J.,
et al
.
Pure
Appl. Chem.
, 2000,
72
, 1207.
5.
Trost, B. M.
Science
, 1991,
254
, 1471.
6.
Trost, B. M.
Angew. Chem., Int. Ed. Engl.
, 1995,
34
, 259.
7.
Sheldon, R. A.
Chemtech
, 1994,
24
, 38.
8.
Sheldon, R. A.
J. Mol. Catal. A: Chem.
, 1996,
107
, 75.
9.
Sheldon, R. A.
J. Chem. Technol. Biotechnol.
, 1997,
68
,
381.
10.
Sheldon, R. A.
C. R. Acad. Sci., Ser. IIc: Chim.
, 2000,
3
,
541.
11.
Repic, O.
Process Research and Chemical Development in
the Pharmaceutical Industry
. John Wiley, New York,
1998.
12.
Lee, S., & Robinson, G.
Process Development: Fine Chem-
icals from Grams to Kilograms
. Oxford University Press,
Oxford, 1995.
13.
Jones, D. G.
Chemistry and Industry. Applications of Basic
