Development of an SNAr Reaction: A Practical and Scalable Strategy To Sequester and Remove HF

被引：11

作者：

Blacker, A. John ^{[1
,2
]}

Moran-Malagon, Gabriel ^{[1
,2
]}

Powell, Lyn ^{[3
]}

Reynolds, William ^{[1
,2
]}

Stones, Rebecca ^{[1
,2
]}

Chapman, Michael R. ^{[1
,2
]}

机构：

[1] Univ Leeds, Inst Proc Res & Dev, Sch Chem, Leeds LS2 9JT, W Yorkshire, England

[2] Univ Leeds, Sch Chem & Proc Engn, Leeds LS2 9JT, W Yorkshire, England

[3] AstraZeneca, Chem Dev, Macclesfield SK10 2NA, Cheshire, England

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2018年 / 22卷 / 09期

基金：

英国工程与自然科学研究理事会;

关键词：

SNAr reaction; calcium fluoride; aryl amines; fluoride sequestration; scale-up; NUCLEOPHILIC-SUBSTITUTION; BIOLOGICAL EVALUATION; PHYSICAL-PROPERTIES; HYDROFLUORIC-ACID; DERIVATIVES; DESIGN; AMINATION; PIPERAZINES; INHIBITOR; CHEMISTRY;

D O I：

10.1021/acs.oprd.8b00090

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A simple and operationally practical method to sequester and remove fluoride generated through the SNAr reaction between amines and aryl fluorides is reported. Calcium propionate acts as an inexpensive and environmentally benign in situ scrubber of the hydrofluoric acid byproduct, which is simply precipitated and filtered from the reaction mixture during standard aqueous workup. The method has been tested from 10 to 100 g scale of operation, showing >99.5% decrease in fluoride content in each case. Full mass recovery of calcium fluoride is demonstrated at both scales, proving this to be a general, efficient, and robust method of fluoride abstraction to help prevent corrosion of glass-lined reactors.

引用

页码：1086 / 1091

页数：6

共 29 条

[1]

[Anonymous], 2004, DEANS ANALYTICAL CHE

[2] Design, synthesis, and biological evaluation of prazosin-related derivatives as multipotent compounds [J].

Antonello, A ;

Hrelia, P ;

Leonardi, A ;

Marucci, G ;

Rosini, M ;

Tarozzi, A ;

Tumiatti, V ;

Melchiorre, C .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (01) :28-31

[3] NUCLEOPHILIC-SUBSTITUTION - LINEAR FREE-ENERGY RELATIONSHIPS BETWEEN REACTIVITY AND PHYSICAL-PROPERTIES OF LEAVING GROUPS AND SUBSTRATES [J].

BARTOLI, G ;

TODESCO, PE .

ACCOUNTS OF CHEMICAL RESEARCH, 1977, 10 (04) :125-132

[4]

Bretherick L, 1990, BRETHERICKS HDB REAC, P299

[5] Advances in the design and synthesis of prazosin derivatives over the last ten years [J].

Desiniotis, Andreas ;

Kyprianou, Natasha .

EXPERT OPINION ON THERAPEUTIC TARGETS, 2011, 15 (12) :1405-1418

[6] Synthesis and antibacterial activity of levofloxacin derivatives with certain bulky residues on piperazine ring [J].

Foroumadi, Alireza ;

Emami, Saeed ;

Mansouri, Shahla ;

Javidnia, Azita ;

Saeid-Adeli, Nosratollah ;

Shirazi, Farshad H. ;

Shafiee, Abbas .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2007, 42 (07) :985-992

[7] AZD4547: An Orally Bioavailable, Potent, and Selective Inhibitor of the Fibroblast Growth Factor Receptor Tyrosine Kinase Family [J].

Gavine, Paul R. ;

Mooney, Lorraine ;

Kilgour, Elaine ;

Thomas, Andrew P. ;

Al-Kadhimi, Katherine ;

Beck, Sarah ;

Rooney, Claire ;

Coleman, Tanya ;

Baker, Dawn ;

Mellor, Martine J. ;

Brooks, A. Nigel ;

Klinowska, Teresa .

CANCER RESEARCH, 2012, 72 (08) :2045-2056

[8]

Hartwig J.F., 2007, PATAI'S Chemistry of Functional Groups, P455, DOI DOI 10.1002/CHIN.200732252

[9] An improved ruthenium catalyst for the environmentally benign amination of primary and secondary alcohols [J].

Hollmann, Dirk ;

Tillack, Annegret ;

Michalik, Dirk ;

Jackstell, Ralf ;

Beller, Matthias .

CHEMISTRY-AN ASIAN JOURNAL, 2007, 2 (03) :403-410

[10] Tricyclic pharmacophore-based molecules as novel integrin αvβ3 antagonists.: Part 1:: Design and synthesis of a lead compound exhibiting αvβ3/αIIbβ3 dual antagonistic activity [J].

Kubota, D ;

Ishikawa, M ;

Yamamoto, M ;

Murakami, S ;

Hachisu, M ;

Katano, K ;

Ajito, K .

BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (07) :2089-2108

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