Tuesday, 5 January 2016
4-Chlorobenzo[b]thiophene a key intermediate in brexpiprazole synthesis
We established an improved synthetic route to 4-chlorobenzo[b]thiophene, a key intermediate in brexpiprazole synthesis, via a practical decarboxylation process in three steps. Thermal analysis demonstrated that the coexistence of the decarboxylated product with DBU should be avoided and that removal of the product outside the reactor was vital. Our process yields the target compound by distillation under reduced pressure and is safe, highly batch efficient, cost-effective, and high yielding. Furthermore, manufacturing on a pilot scale was also accomplished through our approach.
4-Chlorobenzo[b]thiophene-2-carboxylic Acid (4)
4 as a white solid
mp 260 °C.
1H NMR (300 MHz, DMSO-d6) δ 7.54 (d, 1H, J = 11.6, 7.7 Hz), 7.56 (dd, 1H, J = 17.8, 7.7 Hz), 8.03 (d, 1H, J = 0.7 Hz), 8.07 (td, 1H, J = 7.6, 0.9 Hz), 13.19 (brs, 1H).
13C NMR (75 MHz, DMSO-d6) δ 122.21, 125.01, 126.84, 127.99, 128.96, 136.50, 136.57, 142.55, 163.10.
Elemental analysis calcd for C: 50.83%, H: 2.37%, found C: 50.84%, H: 2.21%.
2,3,4,6,7,8,9,10-Octahydropyrimido[1,2-a]azepin-1-ium 4-Chlorobenzo[b]thiophene-2-carboxylate 5
5 as a white solid
Mp 182.5 °C.
1H NMR (300 MHz, CDCl3) δ 1.66 (m, 6H), 1.80–1.75 (m, 2H), 2.98–2.94 (m, 2H), 3.45–3.39 (m, 4H), 3.55–3.51 (m, 2H), 7.31–7.20 (m, 2H), 7.69 (dd, 1H, J = 3.9, 0.6 Hz), 7.97 (s, 1H), 13.19 (brs, 1H).
13C NMR (75 MHz, CDCl3) δ 19.51, 24.03, 26.70, 28.88, 31.99, 38.01, 48.36, 53.94, 121.04, 123.00, 125.17, 126.61, 128.98, 138.21, 142.43, 146.85, 165.91, 167.20.
Elemental analysis calcd for C: 59.25%, H: 5.80%, N: 7.68%, found C: 59.10%, H: 5.44%, N: 7.53%.
4-Chlorobenzo[b]thiophene (2)
1H NMR (300 MHz, CDCl3) δ 7.26 (t, 1H, J = 7.8 Hz), 7.36 (dd, 1H, J = 7.8, 0.9 Hz), 7.50 (d, 1H, J = 5.7 Hz), 7.52 (d, 1H, J = 5.7 Hz), 7.76 (d, 1H, J = 7.8 Hz).
13C NMR (75 MHz, CDCl3) δ 121.12, 122.40, 125.02, 127.43, 128.93, 138.06, 141.07.
Elemental analysis calcd for C: 56.98%, H: 2.99%, found C: 56.76%, H: 2.94%.
SEE
http://pubs.acs.org/doi/abs/10.1021/acs.oprd.5b00340
http://pubs.acs.org/doi/suppl/10.1021/acs.oprd.5b00340/suppl_file/op5b00340_si_001.pdf
Safe and Efficient Decarboxylation Process: A Practical Synthetic Route to 4-Chlorobenzo[b]thiophene
Bulk Pharmaceutical Chemicals Department,
Second Tokushima Factory, Production Headquarters, Otsuka Pharmaceutical
Co., Ltd., 224-18, Hiraishi Ebisuno, Kawauchi-cho, Tokushima 771-0182, Japan
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.5b00340
Monday, 4 January 2016
4-Chlorobenzo[b]thiophene-2-carboxylic Acid
4-Chlorobenzo[b]thiophene-2-carboxylic acid; 23967-57-9; 4-chloro-1-benzothiophene-2-carboxylic acid; GA-0943; 4-chloro-benzo[b]thiophene-2-carboxylic acid;
4-Chlorobenzo[b]thiophene-2-carboxylic Acid
4 as a white solid
mp 260 °C.
1H NMR (300 MHz, DMSO-d6) δ 7.54 (d, 1H, J = 11.6, 7.7 Hz), 7.56 (dd, 1H, J = 17.8, 7.7 Hz), 8.03 (d, 1H, J = 0.7 Hz), 8.07 (td, 1H, J = 7.6, 0.9 Hz), 13.19 (brs, 1H).
13C NMR (75 MHz, DMSO-d6) δ 122.21, 125.01, 126.84, 127.99, 128.96, 136.50, 136.57, 142.55, 163.10.
Elemental analysis calcd for C: 50.83%, H: 2.37%, found C: 50.84%, H: 2.21%.
SEE
http://pubs.acs.org/doi/abs/10.1021/acs.oprd.5b00340
http://pubs.acs.org/doi/suppl/10.1021/acs.oprd.5b00340/suppl_file/op5b00340_si_001.pdf
Safe and Efficient Decarboxylation Process: A Practical Synthetic Route to 4-Chlorobenzo[b]thiophene
Bulk Pharmaceutical Chemicals Department,
Second Tokushima Factory, Production Headquarters, Otsuka Pharmaceutical
Co., Ltd., 224-18, Hiraishi Ebisuno, Kawauchi-cho, Tokushima 771-0182, Japan
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.5b00340
Sunday, 3 January 2016
Palladium(II) porphyrin – anthracene dyad bridged via short and conformationally rigid bicyclo[2.2.2]octadiene spacer
.Compound 2
The synthesis and photophysical characterization of a palladium(II) porphyrin – anthracene dyad bridged via short and conformationally rigid bicyclo[2.2.2]octadiene spacer were achieved. A spectroscopic investigation of the prepared molecule in solution has been undertaken to study electronic energy transfer in excited singlet and triplet states between the anthracene and porphyrin units. By using steady-state and time-resolved photoluminescence spectroscopy it was shown that excitation of the singlet excited state of the anthracene leads to energy transfer to the lower-lying singlet state of porphyrin. Alternatively, excitation of the porphyrin followed by intersystem crossing to the triplet state leads to very fast energy transfer to the triplet state of anthracene. The rate of this energy transfer has been determined by transient absorption spectroscopy. Comparative studies of the dynamics of triplet excited states of the dyad and reference palladium octaethylporphyrin (PdOEP) have been performed.
SEE..................
http://pubs.rsc.org/en/content/articlelanding/2015/dt/c5dt03784k#!divAbstract
Paper
Interplay between singlet and triplet excited states in a conformationally locked donor–acceptor dyad
*
Corresponding authors
a
Max Planck
Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany
E-mail: filatovm@tcd.ie
E-mail: filatovm@tcd.ie
Mikhail A Filatov
b
Institute of
Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., block
103-A, BG – 1113 Sofia, Bulgaria
c
Physical Sciences
and Engineering Division (PSE), Material Science and Engineering (MSE),
Solar and Photovoltaics Engineering Research Center (SPERC), King
Abdullah University of Science and Technology (KAUST), Thuwal
23955-6900, Kingdom of Saudi Arabia
d
Optics and
Spectroscopy Department, Faculty of Physics, Sofia University “St.
Kliment Ochridski”, 5 James Bourchier, 1164 Sofia, Bulgaria
e
Freiburg Institute
for Advanced Studies (FRIAS), Albert-Ludwigs-Universität Freiburg,
Albertstraße 19, D-79104 Freiburg, Germany
Dalton Trans., 2015,44, 19207-19217
DOI: 10.1039/C5DT03784K
Mikhail A Filatov
Research Experience
Subscribe to:
Posts (Atom)