CAS: 37098-75-2; 5-(Chlorosulfonyl)-2-Fluorobenzoic Acid

上下游产品

CAS号445-29-4 邻氟苯甲酸 | CAS号247569-56-8 2-氟-5-(甲基磺酰基)苯甲酸 | CAS号112887-25-9 2-氟-5-磺酰胺苯甲酸

邻氟苯甲酸置于氯磺酸体系中,化学反应 14.0H,以74%的收率获得产物5-(氯磺酰基)-2-氟苯甲酸
参考文献:通过相转移催化的2-卤代-5-(氨磺酰基)苯甲酸的亲核芳香取代和n,O-双烷基化:Rorγ反向激动剂gsk2981278A的合成
标题:通过相转移催化的2-卤代-5-(氨磺酰基)苯甲酸的亲核芳香取代和n,O-双烷基化:Rorγ反向激动剂gsk2981278A的合成
摘要:Gsk2981278A(1)是一种rorγ反向激动剂,可用作牛皮癣的潜在局部非类固醇疗法.基于(四氢-2 H-吡喃-4-基)甲醇与由2-卤代苯甲酸制备的芳基卤化物中间体的s N Ar反应,开发了1的新合成方法.该二价阴离子进行原位n,O-双-异丁基化,然后还原得到1.新路线消除了(四氢-2 H-吡喃-4-基)甲醇的对甲苯磺酸的遗传毒性,并从水杨酸甲酯开始的原始合成中进行了困难的还原胺化.该路线的主要版本已扩大规模,可提供125公斤的1.但是,发现在双烷基化过程中在dmso中长时间加热强碱是制造过程中的安全隐患.然后,利用容易的n,O-双-烷基化开发了一种更安全,更环保的方法,该方法在相转移条件下,使用温和的碱(例如碳酸钾),并在绿色溶剂(例如水)中进行.从2-卤代苯甲酸到gsk2981278A(1)的简洁的四个阶段序列的总产率为41%.
DOI:10.1021/acs.Oprd.9B00147

专利信息

专利号:US-7812161-B2
优先权日:2007-03-05
标 题 :Synthesis of GlyT-1 inhibitors
发明人：PFLEGER CHRISTOPHE; WALDMEIER PIUS; WANG SHAONING
权利人:HOFFMANN LA ROCHE
摘要:The present invention relates to a process for preparation of a compound of formula I n nwhereinn Het, R 1 , R 2 , R 3 , and n are as defined herein and pharmaceutically acceptable acid addition salts thereof, which comprises reacting a compound of formula 21 with a compound of formula 8 to obtain a compound of formula 11 and coupling the compound of formula 11 in the presence of a coupling reagent or the corresponding acid halogenide with a compound of formula 15 to obtain a compound of formula I.

专利号:WO-2008107334-A2
优先权日:2007-03-05
标题:Process for the synthesis of glyt-1 inhibitors

专利号:US-2008221327-A1
优先权日:2007-03-05
标题:Synthesis of glyt-1 inhibitors

专利号:EP-2131843-B1
优先权日:2007-03-05
标题 :Process for the synthesis of glyt-1 inhibitors