RAMELTEON

An efficient and practical process for the synthesis of ramelteon 1, a sedative-hypnotic, is described. Highlights in this synthesis are the usage of acetonitrile as nucleophilic reagent to add to 4,5-dibromo-1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-one 2 and the subsequent hydrogenation which successfully implement four processes (debromination, dehydration, olefin reduction, and cyano reduction) into one step to produce the ethylamine compound 13where dibenzoyl-l-tartaric acid is selected both as an acid to form the salt in the end of hydrogenation and as the resolution agent. Then, target compound 1 is easily obtained from13 via propionylation. The overall yield in this novel and concise process is almost twice as much as those in the known routes, calculated on compound 2.

A Novel and Practical Synthesis of Ramelteon

Sa Xiao , Chao Chen , Hongyan Li , Kuaile Lin , andWeicheng Zhou *

State Key Lab of New Drug & Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, State Institute of Pharmaceutical Industry, Shanghai 200437,China

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/op500386g

http://pubs.acs.org/doi/abs/10.1021/op500386g

Publication Date (Web): January 6, 2015

Copyright © 2015 American Chemical Society

*Telephone: +86 21 55514600. E-mail: zhouweicheng58@163.com.

NMR, IR MASS………http://pubs.acs.org/doi/suppl/10.1021/op500386g/suppl_file/op500386g_si_001.pdf

Preparation of (S)-N-[2-(1,6,7,8-Tetrahydro-2H-indeno[5,4-b] furan-8-yl)ethyl]propionamide(1).

GAVE

white solid of 1(1.570 g, 85% yield, 99.8% ee). Purity by HPLC 99.6%.

Mp: 115−116 °C(113−115°C in literature 1 ).

1 H−NMR(400 MHz, CDCl3):

δ 1.39 (t, 3H); 1.63 (m, 1H); 1.83 (m, 1H); 2.02 (m, 1H); 2.16 (dd, J=8, 2H); 2.28 (m, 1H); 2.78 (m, 1H); 2.83 (m, 1H); 3.14 (m, 1H); 3.22 (m, 2H); 3.33 (m, 2H); 4.54 (m, 2H); 5.38 (br s, 1H); 6.61 (d, J=8, 1H); 6.97 (d, J=8, 1H).

13C−NMR(100 MHz, CDCl3):

δ 173.85, 159.56, 143.26, 135.92, 123.52, 122.28, 107.56, 71.26, 42.37, 38.17, 33.66, 31.88, 30.82, 29.86, 28.73, 10.01.

MS (ES+): m/z 282(M+Na) + .

[α]D −57.3(c=1.0, CHCl3, −57.8 in literature 1 ).

Anal. (C16H21NO2) Calc: C, 74.10; H, 8.16; N, 5.40; found: 74.09; H, 8.17; N, 5.47.

References

(1) Uchikawa, O.; Fukatsu, K.; Tokunoh, R.; Kawada, M.; Matsumoto, K.; Imai, Y.; Hinuma, S.; Kato, K.; Nishikawa, H.; Hirai, K.; Miyamoto M.; Ohkawa, S. J. Med. Chem. 2002, 45, 4222-4239.

(2) Yamano, T.; Yamashita, M.; Adachi, M.; Tanaka, M.; Matsumoto, K.; Kawada, M.; Uchikawa, O.; Fukatsu, K.; Ohkawa, S. Tetrahedron: Asymmetry. 2006, 17, 184-190.

SHANGHAI

SHANGHAI CHINA

The Shanghai International Exhibition Center, an example of Soviet neoclassical architecture in Shanghai

Bulletin of the Chemical Society of Ethiopia

http://www.ajol.info/index.php/bcse


\

Federal Democratic Republic of Ethiopia የኢትዮጵያ ፌዴራላዊ ዲሞክራሲያዊ ሪፐብሊክ ye-Ītyōṗṗyā Fēdēralāwī Dīmōkrāsīyāwī Rīpeblīk
Flag Emblem

Coins of the Axumite king Endybis, 227–235 AD, at the British Museum. The inscriptions in Ancient Greek read "AΧWMITW BACIΛEYC" ("King of Axum") and "ΕΝΔΥΒΙC ΒΑCΙΛΕΥC" ("King Endybis").

Mountain nyalas in Nechisar National Park, one of several wildlife reserves in Ethiopia.

EXAMPLE


Journal Home > Vol 29, No 1 (2015) > 

Regioselective iodination of aryl amines using 1,4-dibenzyl-1,4-diazoniabicyclo [2.2.2] octane dichloroiodate in solution and under solvent-free conditions

M. Alikarami, S. Nazarzadeh, M. Soleiman-Beigi

Abstract

1,4-Dibenzyl-1,4-diazoniabicyclo[2.2.2]octane dichloroiodate is an efficient and regioselective reagent for iodination of aryl amines. A wide variety of aryl amines in reaction with this reagent afforded regioselectively iodinated products. The iodination reaction can be carried out in solution or under solvent-free condition at room temperature.

KEY WORDS:  Regioselective iodination, Aryl amines, 1,4-Dibenzyl-1,4-diazoniabicyclo [2.2.2] octane dichloroiodate,  Solvent-free conditions

Bull. Chem. Soc. Ethiop. 2015, 29(1), 157-162

DOI: http://dx.doi.org/10.4314/bcse.v29i1.15

Full Text:

EMAIL FREE FULL TEXT 
DOWNLOAD FULL TEXT

"Pd/NHC-Catalyzed Enantiospecific and Regioselective Suzuki-Miyaura Arylation of 2-Arylaziridines: Synthesis of Enantioenriched 2-Arylphenethylamine Derivatives"

"Pd/NHC-Catalyzed Enantiospecific and Regioselective Suzuki-Miyaura Arylation of 2-Arylaziridines: Synthesis of Enantioenriched 2-Arylphenethylamine Derivatives"
Youhei Takeda*, Yuki Ikeda, Akinobu Kuroda, Shino Tanaka, and Satoshi Minakata*
J. Am. Chem. Soc. 2014, 136, 8544–8547. DOI: 10.1021/ja5039616 

* Highlighted in Org. Process Res. Dev. as "Some Items of Interest to Process R&D Chemists and Engineers"! !（link）
Abstract: A palladium-catalyzed stereospecific and regioselective cross-coupling of enantiopure 2-arylaziridines with arylboronic acids under mild conditions to construct a tertiary stereogenic center has been developed. N-heterocyclic carbene (NHC) ligands drastically promote the coupling, suppressing β-hydride elimination. The enantiospecific cross-coupling allowed us for preparation of a series of biologically important 2-arylphenethylamine derivatives in an enantiopure form.

Utilization of N－X bonds in the synthesis of N-heterocycles

Utilization of N－X bonds in the synthesis of N-heterocycles

Simple nitrogen-containing heterocycles could be constructed from carbon-carbon double bond (including fulleren) as carbon resources.

Acc. Chem. Res. 2009, 42, 1172

Application of carbon dioxide to organic synthesis

Application of carbon dioxide to organic synthesis

Carbon dioxide fixation to unsaturated alcohols could be realized under extremely mild conditions by using tert-BuOI.



Angew. Chem. Int. Ed. 2010, 49, 1309.


Haloamidation of olefins induced by carbon dioxide was developed.

Org. Lett. 2006, 8, 967.　Org. Bio.mol. Chem. 2010, 8, 1424

Application of water/silica system to organic synthesis

Application of water/silica system to organic synthesis

Organic reactions on silica in water were successfully achieved by utilizing hydrophobic interaction.

Chem. Rev. 2009, 109, 711.　Angew. Chem. Int. Ed. 2004, 43, 79

(R)-(−)-2-[(5-oxido-5-phenyl-5λ4-isoquino[4,3-c][2,1]benzothiazin- 12-yl)amino]benzonitrile (4).



Copper-catalyzed cross-coupling between (S)-S-methyl-S-phenylsulfoximine (1) and 2-iodobenzonitrile (2) resulted in the discovery of an unprecedented one-pot triple arylation sequence to give (R)-(−)-2-[(5-oxido-5-phenyl-5λ4-isoquino[4,3-c][2,1]benzothiazin- 12-yl)amino]benzonitrile (4). Here, we describe the synthesis of the title compound (R)-4 and the elucidation of its structure by means of various techniques.

Molbank 2014, 2014(3), M834; doi:10.3390/M834

http://www.mdpi.com/1422-8599/2014/3/M834

(R)-(−)-2-[(5-Oxido-5-phenyl-5λ⁴-isoquino[4,3-c][2,1]benzothiazin-12-yl)amino]benzonitrile

Marcus Frings, Iuliana Atodiresei and Carsten Bolm * 

* Author to whom correspondence should be addressed; E-Mail: carsten.bolm@oc.rwth-aachen.de;

Fax: +29-241-80-92-391. http://bolm.oc.rwth-aachen.de/

Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany

 Carsten Bolm

   Dr. rer. nat., Professor of Organic Chemistry

Institut für Organische Chemie
RWTH Aachen University
Landoltweg 1
D-52074 Aachen, Germany 

Tel.: + 49 241-80 94 675
FAX : + 49 241-80 92 391 

e-mail: Carsten.Bolm@oc.RWTH-Aachen.de

http://bolm.oc.rwth-aachen.de/

The combined organic phases were dried with

MgSO4 and filtered. After evaporation of solvents, the oily residue was subjected to column

chromatography (SiO2, n-pentane/EtOAc = 2/1). Product (R)-4 was isolated as a yellow solid.

Additionally, sulfoximine (S)-3 was separately obtained as a yellow oil (61% yield, 0.899 g, 3.51 mmol).

Yield: 23% (0.616 g, 1.34 mmol); mp = 211–212 °C (racemate: 263–265 °C); [α] = −57.7 (c = 0.6 g,

100 mL−1, CHCl3); 1H NMR (600 MHz, CDCl3): δ = 7.11 (ddd, J = 8.2 Hz, 7.1 Hz, 1.2 Hz, 1H, Ar-H),

7.25 (dd, J = 8.0 Hz, 1.1 Hz, 1H, Ar-H), 7.27 (td, J = 7.6 Hz, 1.0 Hz, 1H, Ar-H), 7.42–7.50 (m, 3H,

Ar-H), 7.50–7.58 (m, 3H, Ar-H), 7.70 (dd, J = 7.8 Hz, 1.5 Hz, 1H, Ar-H), 7.78 (ddd, J = 8.8 Hz, 7.5

Hz, 1.6 Hz, 1H, Ar-H), 7.87–7.90 (m, 2H, Ar-H), 8.07 (dd, J = 7.6 Hz, 1.6 Hz, 1H, Ar-H), 8.19–8.24

(m, 2H, Ar-H and NH), 8.50 (dd, J = 8.1 Hz, 1.5 Hz, 1H, Ar-H), 8.81 (d, J = 8.4 Hz, 1H, Ar-H) ppm;

13C NMR (150 MHz, CDCl3): δ = 103.4 (C), 105.5 (Ar-C), 116.9 (Ar-C), 117.5 (C), 118.4 (Ar-C),

120.3 (Ar-CH), 121.8 (Ar-CH), 122.3 (Ar-CH), 123.6 (Ar-CH), 123.8 (Ar-CH), 124.8 (Ar-CH), 125.9

(Ar-CH), 127.6 (Ar-CH), 127.7 (2 Ar-CH), 129.0 (2 Ar-CH), 132.0 (2 Ar-CH), 132.4 (Ar-CH), 132.5

(Ar-C), 132.8 (Ar-CH), 133.9 (Ar-CH), 141.7 (Ar-C), 144.0 (Ar-C), 144.2 (Ar-C), 148.0 (C), 153.2

(C) ppm; 1

H NMR [600 MHz, (CD3)2SO]: δ = 6.98 (ddd, J = 8.2 Hz, 7.2 Hz, 1.1 Hz, 1H, Ar-H), 7.11

(dd, J = 8.1 Hz, 0.8 Hz, 1H, Ar-H), 7.40 (ddd, J = 8.6 Hz, 7.2 Hz, 1.6 Hz, 1H, Ar-H), 7.53 (td, J = 7.7 Hz,

1.0 Hz, 1H, Ar-H), 7.56–7.60 (m, 2H, Ar-H), 7.60–7.64 (m, 1H, Ar-H), 7.67–7.73 (m, 2H, Ar-H), 7.80

(d, J = 8.0 Hz, 1H, Ar-H), 7.84–7.88 (m, 3H, Ar-H), 8.04 (dd, J = 7.8 Hz, 1.4 Hz, 1H, Ar-H), 8.12 (dd,

J = 7.7 Hz, 1.8 Hz, 1H, Ar-H), 8.18 (dd, J = 8.1 Hz, 1.5 Hz, 1H, Ar-H), 8.68 (dd, J = 7.5 Hz, 1.7 Hz,

1H, Ar-H), 10.51 (s, 1H, NH) ppm; 

13C NMR [150 MHz, (CD3)2SO]: δ = 103.5 (C), 110.2 (Ar-C),

117.0 (Ar-C), 117.4 (C), 118.0 (Ar-C), 119.7 (Ar-CH), 122.6 (Ar-CH), 123.6 (Ar-CH), 124.5 (Ar-CH),

125.6 (Ar-CH), 126.2 (Ar-CH), 127.1 (2 Ar-CH), 127.3 (Ar-CH), 127.4 (Ar-CH), 129.3 (2 Ar-CH), 

131.7 (Ar-C), 131.8 (Ar-CH), 132.2 (Ar-CH), 133.0 (Ar-CH), 133.1 (Ar-CH), 133.9 (Ar-CH), 141.9

(Ar-C), 143.7 (Ar-C), 144.0 (Ar-C), 147.4 (C), 155.6 (C) ppm; 

IR (ATR): ν = 3640, 3258, 2324, 2221,

2020, 1980, 1936, 1601, 1572, 1546, 1515, 1484, 1459, 1422, 1376, 1333, 1277, 1241, 1206, 1149,

1092, 1038, 1009, 976, 844, 794, 754, 720, 681 cm−1; EI-MS: m/z (%) = 458 (100) [M]+, 410 (15), 381(22), 357 (9), 333 (62), 102 (6), 77 (12), 51 (10); CI-MS: m/z (%) = 499 (3) [M+C3H5]+, 487 (16)[M+C2H5]+

, 459 (100) [M+H]+, 358 (7); ESI-MS: m/z (%) = 939 (9) [2M+Na]+, 497 (8) [M+K]+, 481(24) [M+Na]+, 459 (42) [M+H]+, 358 (100); ESI-HRMS: m/z calcd for C28H19N4OS: 459.12741; found

459.12793 with ∆ = 1.14 ppm; anal. calcd for C28H18N4OS (458.54): C, 73.34; H, 3.96; N, 12.22;

found C, 73.44; H, 4.09; N, 12.30; HPLC: tr = 16.8 min [major], tr = 25.2 min [minor] (Chiralpak AD-H,

0.6 mL min−1, n-heptane/isopropanol = 60/40, λ = 230 nm, 20 °C); >99% ee.

Crystallographic data were collected with a Bruker Kappa APEX II CCD-diffractometer with

monochromatic Mo–Kα radiation (λ = 0.71073 Å) and a CCD detector. The structure was solved by

direct methods using SHELXS-97 and refined against F2 on all data by full-matrix least-squares

methods using SHELXL-97 [13,14]. 

Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany

GERMANY....