Carfentanyl
525
during this step. Workers should wear protective equipment, including appropriate
gloves and eye protection.
Methyl 4-(phenylamino)-1-(2-phenylethyl)-4-piperidinecarboxylate (3)
ꢀ
Methanol (65 ml) was poured into a 250 ml round bottom flask and cooled to 0 C in an
ice bath. Trifluorormethanesulfonic acid (11.5 ml) was added dropwise to the MeOH
with intensive stirring and cooling (Caution: Very corrosive vapors and liquid! Greatly
exothermic process!). After the addition of CF SO H was complete, the ice bath was
3
3
removed and 2.2 ml DMSO was added, followed by the addition of 3.16 g amide (2).
The reaction mixture was refluxed and monitored by TLC (DCM:MeOH, 8:1) until the
starting material was mostly consumed (after about 4 days of refluxing), about 90%
conversion. The reaction mixture was cooled down to room temperature and slowly
poured into 300 ml of 10% aqueous K CO . The mixture was transferred to a separatory
2
3
funnel and the product was extracted with 6 x 50 ml EtOAc. Combined extracts were
washed with 2 x 50 ml aq. NaHCO solution, followed by drying over anhydrous
3
Na SO and removal of the volatiles under reduced pressure. The obtained crude prod-
2
4
uct was purified by flash chromatography on silica gel with DCM:EtOAc:iPrOH 6:2:1.
Methyl 4-(phenylamino)-1-(2-phenylethyl)-4-piperidinecarboxylate (2.09 g) was
ꢀ
6
ꢀ
obtained in 65% yield as a creamy white solid, mp. 92-94 C, lit. mp. 94.9 C; Rf
1
¼
0.5; H NMR (700 MHz, CDCl ) d: 2.08 (d, J ¼ 14.0 Hz, 2H, CH ), 2.30
3
2
(
t, J ¼ 10.5 Hz, Ph-CH -CH -N, 2H), 2.54 (t, J ¼ 10.5 Hz, Ph-CH -CH -N, 2H), 2.64 -
2
2
2
2
2
3
-
.66 (m, 2H, CH ), 2.73 (s, CH , 2H), 2.81–2.83 (m, CH , 2H), 3.69 (s, COOCH , 3H),
2 2 2 3
.87 (s, NH, 1H), 6.58 (d, J¼ 8.4 Hz, Ar(H), 2H), 6.76 (t, J¼ 7.7 Hz, Ar(H), 1H), 7.14
13
7.16 (m, Ar(H), 2H), 7.19 - 7.21 (m, Ar(H), 3H), 7.25 - 7.29 (m, Ar(H), 2H).
C
NMR (125 MHz, CDCl ) d: 32.86, 33.56, 48.99, 52.36, 58.17, 60.30, 115.51, 118.87,
3
1
26.16, 128.45, 128.69, 129.17, 139.99, 144.85, 175.68.
ORCID
Eerold Vellem €a e
Anton Mastitski
Jaak J €a rv
Jukka Veli Hiltunen
References
1
2
3
4
5
6
. R. S. Vardanyan and V. J. Hruby, Fut. Med Chem., 6, 385 (2014).
. T. F. Meert, Pharm. World Sci., 18, 1 (1996).
. A. Poklis, Clin. Toxicol., 33, 439 (1995).
. L. E. Mather, Clin. Pharmacokinet., 8, 422 (1983).
. S. Yang and Q. Xu, Shanghai Yiyao, 36, 32 (2015).
. P. G. Van Daele, M. F. de Bruyn, J. M. Boey, S. Sanczuk, J. T. Agten and P. A. Janssen,
Arzneim.-Forsch., 26, 1521 (1976).
7
. J. C. Haigh, L. J. Lee, and R. E. Schweinsburg, J. Wildl. Dis., 19, 140 (1983).