- Preparation method of (S)-1-tert-butyloxycarbonyl-3-hydroxypiperidine
-
The invention discloses a preparation method of (S)-1-tert-butyloxycarbonyl-3-hydroxypiperidine, and relates to the technical field of biological pharmacy. The preparation method comprises the following steps: 1, preparing 3-hydroxypyridine (2) as a raw material; 2, preparing racemic 3-hydroxypiperidine (3) from 3-hydroxypyridine (2); 3, preparing a derivative (2S, 3S)-N-(4-chlorphenyl)-2, 3-dihydroxy succinamic acid (4) from racemic 3-hydroxypiperidine (3) and D-tartaric acid; 4, carrying out resolution reaction on the derivative (2S, 3S)-N-(4-chlorphenyl)-2, 3-dihydroxy succinamic acid (4) prepared from D-tartaric acid to obtain a (S)-hydroxypiperidine salt (5); and 5, subjecting an obtained mixture to extraction, concentration and crystallization, to prepare a (S)-1-tert-butyloxycarbonyl-3-hydroxypiperidine salt (5). The preparation process has the advantages that the synthesis steps are reduced, the yield is increased, an adopted chiral resolving agent can be recycled, and the preparation process is suitable for industrial production.
- -
-
Paragraph 0025; 0027; 0034; 0037; 0044; 0047; 0055; 0058
(2020/03/25)
-
- Enantioenriched N-(2-Chloroalkyl)-3-acetoxypiperidines as Potential Cholinotoxic Agents. Synthesis and Preliminary Evidence for Spirocyclic Aziridinium Formation.
-
The syntheses of six enantioenriched analogs representing cyclic forms of acetylcholine are reported. (S)- and (R)-N-(2-chloroethyl)-3-acetoxypiperidine and (R,R)-, (R,S)-, (S,R)-, and (S,S)-N-(2-chloropropyl)-3-acetoxypiperidine have been synthesized from (R)- or (S)-3-hydroxypiperidine in five steps. (R)- and (S)-3-hydroxypiperidine were accessed via parallel stereospecific routes from d- and l-glutamic acid, and through fractional recrystallization of diastereomeric tartranilic acid salts. (S)-N-(2-Chloroethyl)-3-acetoxypiperidine was reacted with silver perchlorate to form a spirocyclic aziridinium analog of acetylcholine as evidenced by a characteristic 1H NMR shift for the aziridinium methylene groups.
- Huh, Nam,Thompson, Charles M.
-
p. 5935 - 5950
(2007/10/02)
-
- Synthesis and pharmacological activity of stereoisomers of 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 1-(phenylmethyl)-3-piperidinyl ester
-
1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 1-(phenylmethyl)-3-piperidinyl ester 1, a highly potent calcium antagonist, was separated into stereo- and optical isomers to investigate the differences of antihypertensive activities between them. Fractional crystallization of the hydrochlorides of 1 gave α- and β-diasterioisomers. The α-isomer (benidipine hydrochloride, KW-3049) showed very strong hypotensive effect, but little activity was observed in the β-isomer. From optically resolved 1,4-dihydro-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridi necarboxylic acids 2, and 1-benzyl-3-piperidinols 3, four optical isomers of 1 were synthesized, and their absolute configurations were deduced. The hypotensive activity of (+)-α, namely (S)-(S)-1, was 30 to 100 times stronger than that of (-)-α in intravenously administered spontaneously hypertensive rats.
- Muto,Kuroda,Kawato,Karasawa,Kubo,Nakamizo
-
p. 1662 - 1665
(2007/10/02)
-
