89646-44-6Relevant articles and documents
Optical resolution of a 1,5-benzothiazepine derivative, a synthetic intermediate of diltiazem, by preferential crystallization and diastereomeric salt formation
Yamada, Shin-Ichi,Yoshioka, Ryuzo,Shibatani, Takeji
, p. 1922 - 1927 (2007/10/03)
Practical preparation methods of an optically active intermediate of diltiazem, (+)-(2S,3S)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-3-hydroxy-2- (4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one [(+)-7], have been developed by the use of physicochemical and chemical resolutions. 1) The salt of (+)-7 with 3-amino-4-hydroxy-benzenesulfonic acid (AHS), was found to exist as a conglomerate and could be reproducibly resolved into (+)-7·AHS and (-)- 7·AHS of 94-98% ee by a preferential crystallization procedure. 2) (+)- (1R)-3-Bromocamphor-9-sulfonic acid [(+)-BCS] was found to be an efficient resolving agent for (±)-7 and the diastereomeric resolution provided (+)- 7·(+)-BCS·2H2O salt in >43% yield and >97% ee by fractional crystallization. It is presumed that the crystal water of (+)-7·(+)- BCS·2H2O plays an important role in the selective crystallization during this efficient resolution.
Enantiomer associations in the crystal structures of racemic and (2S,3R)-(-)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)- one
Marthi, Katalin,Larsen, Sine,Acs, Maria,Jaszay, Zsuzsa,Fogassy, Elemer
, p. 906 - 913 (2007/10/03)
The crystal structures of racemic and (2S,3R)-(-)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)- one (C16H15NO3S) have been determined in order to compare the interactions between molecules of the same and opposite chirality. The enantiomeric associations observed in these two crystal structures are analysed, relating the differences to those found in the equivalent diastereomers, (2R, 3R) and/or (2S, 3S). Single-crystal X-ray diffraction data were collected at low temperature with Cu Kα radiation (λ = 1.54184 A). Optically active: monoclinic, space group C2, with a = 24.726(3), b = 5.2426(5), c =12.0726(12) A, β - 112.979(9)°, V = 1440.8(5) A3, Z = 4, Dx= 1.389 g cm-3, μ = 20.35 cm-1, the refinement on 2918 observed reflections gave R=0.0271. Racemic: monoclinic, space group P21/n, with a = 13.308(3), b = 4.8474(8), c = 22.130(4) A, β = 91.782(14), V= 1426.9(5) A3, Z=4, Dx= 1.403 g cm-3, μ= 20.54 cm-1, refined to R = 0.0318 for 2753 observed reflections. An intramolecular hydrogen bond between the hydroxy and carbonyl groups appears to stabilize the benzothiazepinone ring in the (P,2S,3R) boat conformation with the hydroxy and methoxyphenyl substituents in equatorial positions. In both crystal structures two N-H...O hydrogen bonds connect the molecules into dimers. In the optically active compound the two molecules are related by a twofold axis, in the racemate by an inversion centre. The racemate contains an additional hydrogen bond which is reflected by its higher melting enthalpy compared with the optically active compound. The difference in the chiral discrimination in the solutions of the cis-and trans-diastereomers does not appear to have its origin in the strong (O-H...O, N-H...O) hydrogen bonds, but rather in the weak (C-H...O) interactions. Acta Chemica Scandinavica 1996.
Stereoselective addition of 2-aminothiophenol to α-alkoxycinnamic acid derivatives - Alternative synthesis of (±)-diltiazem
Miyata, Okiko,Shinada, Tetsuro,Naito, Takeaki,Ninomiya, Ichiya,Date, Tadamasa,Okamura, Kimio
, p. 8119 - 8128 (2007/10/02)
A stereocontrolled synthesis of (±)-diltiazem by applying nucleophilic addition of 2-aminothiophenol to α-alkoxycinnamic acid derivatives is described.
