A concise, stereoselective and scalable synthesis of optically pure (3R,4R)-1-benzyl- and (3R,4R)-1-Boc-3-methyl-4-aminopiperidines

被引：0

作者：

Hazra, Sunit ^{[1
]}

Kangune, Ankit ^{[1
]}

Pawar, Govind ^{[1
]}

Karmakar, Ananta ^{[1
]}

Pabbisetty, Kumar B. ^{[3
]}

Mortensen, Deborah S. ^{[4
]}

Dodd, Dharmpal S. ^{[4
]}

Li, Jianqing ^{[2
]}

Mathur, Arvind ^{[3
]}

Gupta, Anuradha ^{[1
]}

Nimje, Roshan Y. ^{[1
]}

机构：

[1] Biocon Bristol Myers Squibb R&D Ctr, Dept Discovery Synth, Biocon Pk,Plot 2&3,Bommasandra Jigani Rd, Bangalore 560099, India

[2] Bristol Myers Squibb Res & Early Dev, Small Mol Drug Discovery, 200 Cambridge Pk Dr, Cambridge, MA 02140 USA

[3] Bristol Myers Squibb, Small Mol Drug Discovery, POB 4000, Princeton, NJ 08543 USA

[4] Bristol Myers Squibb, 10300 Campus Point Dr Suite 100, San Diego, CA 92121 USA

来源：

TETRAHEDRON | 2024年 / 167卷

关键词：

Concise; Optically pure; (3R; 4R)-3-Methyl-4-aminopiperidines; Scalable; Stereoselective synthesis; DERIVATIVES; FENTANYL; ANALOGS;

D O I：

10.1016/j.tet.2024.134239

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

An efficient, scalable and stereoselective synthesis of optically pure (3R,4R)-1-benzyl- and (3R,4R)-1-Boc-3methyl-4-aminopiperidines has been developed starting from commercially available N-benzyl-3-methyl-4piperidone. The synthesis employed chiral resolution of N-benzyl-3-methyl-4-piperidone, cis-selective reduction of a keto group, and subsequent Mitsunobu inversion of the resulting hydroxy group to install an amine with the desired trans-stereochemistry as the key steps. The method described herein demonstrated a competent route to the title compounds in a cost-effective, and scalable manner.

引用

页数：6

共 50 条

[41] (+)-(3S,4R)-Norcisapride hydrogen (2R,3R)-tartrate monohydrate
Peeters, OM
Blaton, NM
ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, 2002, 58 : O1169 - O1171
[42] Synthetic studies on homophymine A: stereoselective synthesis of (2R,3R,4R,6R)-3-hydroxy-2,4,6-trimethyloctanoic acid
Bellotta, Filomena
D'Auria, Maria Valeria
Sepe, Valentina
Zampella, Angela
TETRAHEDRON, 2009, 65 (18) : 3659 - 3663
[43] Stereoselective synthesis and absolute configuration of (1′R,3R,4R)-4-acetoxy-3-(2′,2′,2′-trifluoro-1′-hydroxyethyl)-azetidin-2-one
Antolini, L
Forni, A
Davoli, P
Moretti, I
Prati, F
TETRAHEDRON-ASYMMETRY, 1998, 9 (02) : 285 - 292
[44] SHORT SYNTHESIS OF (3S,4R)-3-HYDROXY-4-HYDROXYMETHYL-4-BUTANOLIDE AND (3R,4R)-3-HYDROXY-4-HYDROXYMETHYL-4-BUTANOLIDE, 2 LACTONES FROM LEVOGLUCOSENONE
MATSUMOTO, K
EBATA, T
KOSEKI, K
OKANO, K
KAWAKAMI, H
MATSUSHITA, H
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, 1995, 68 (02) : 670 - 672
[45] DIELS-ALDER REACTION OF CHIRAL ACRYLAMIDE AND A CONVENIENT SYNTHESIS OF OPTICALLY PURE METHYL (3R,4R,6R)-BICYCLO[2.2.1]HEPTENE-4-CARBOXYLATE
KISHIKAWA, K
YAMAMOTO, M
KOHMOTO, S
YAMADA, K
CHEMISTRY LETTERS, 1988, (10) : 1623 - 1624
[46] Selection and Scale-Up Evaluation of an Alternative Route to (-)-(3R,4R)-1-Benzyl-4-(benzylamino)piperidin-3-ol
Young, Ian S.
Ortiz, Adrian
Sawyer, James R.
Conlon, David A.
Buono, Frederic G.
Leung, Simon W.
Burt, Justin L.
Sortore, Eric W.
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2012, 16 (09) : 1558 - 1565
[47] MICROBIAL TRANSFORMATION OF CANNABINOIDS .3. MAJOR METABOLITES OF (3R,4R)-DELTA-1-TETRAHYDROCANNABINOL
BINDER, M
POPP, A
HELVETICA CHIMICA ACTA, 1980, 63 (08) : 2515 - 2518
[48] Efficient kinematics of aspherical 4R wrist by means of an equivalent 3R wrist
Bruyninckx, H
Thielemans, H
De Schutter, J
MECHANISM AND MACHINE THEORY, 1998, 33 (06) : 649 - 659
[49] (3R,4R)-3-Methyl-4-decanolide, a Novel Lactone Contributing to Fresh Wasabi (Wasabia japonica) Aroma
Nakanishi, Akira
Miyazawa, Norio
Haraguchi, Kenji
Watanabe, Hiroyuki
Kurobayashi, Yoshiko
Komai, Tsuyoshi
Fujita, Akira
IMPORTANCE OF CHIRALITY TO FLAVOR COMPOUNDS, 2015, 1212 : 99 - 108
[50] Stereoselective synthesis and absolute configuration of (1'R,3R,4R)-4-acetoxy-3-(2',2',2'-trifluoro$ MIN@1'- hydroxyethyl)azetidin-2-one
Antolini, L.
Forni, A.
Davoli, P.
Moretti, I.
Tetrahedron: Asymmetry, 9 (02):

← 1 2 3 4 5 →