114425-49-9

Upstream product

• 20394-86-9 benzylphosphinic acid 
• 541-41-3 chloroformic acid ethyl ester 
• 14684-32-3 ethyl phosphinate 
• 100-39-0 benzyl bromide 

Downstream Products

• 57539-15-8 1-ethoxy-2,2,4-trimethyl-5-phenyl-2,3-dihydro-1H-phosphole 1-oxide 
• 58194-91-5 Benzyl-(phenyl-{N'-[1-phenyl-meth-(E)-ylidene]-hydrazino}-methyl)-phosphinic acid ethyl ester 
• 848773-38-6 C₁₂H₂₁O₂PSi 
• 1027236-48-1 ethyl benzyl(2-cyanoethyl)phosphinate 
• 139668-40-9 ethyl (3-chloro-2(R)-hydroxypropyl)benzylphosphinate 
• 872471-58-4 ethyl (+/-)-4-(tert-butyldimethylsiloxy)cyclopent-1-enyl(benzyl)phosphinate 
• 1017965-04-6 C₃₂H₃₉NO₁₁P₂ 
• 206648-49-9 Ethyl P-benzyl-N-(2,3-dimethoxy-7-nitroquinoxalin-5-ylmethyl)aminomethylphosphinate 
• 1026739-18-3 (3-Amino-propyl)-benzyl-phosphinic acid ethyl ester 

Relevant academic research and scientific papers

DBU-promoted alkylation of alkyl phosphinates and H-phosphonates

The alkylation of alkyl phosphinates and some H-phosphonate diesters is promoted by the base DBU. Only more reactive alkyl halides react in preparatively useful yields. However, the method provides easy access to important H-phosphinate building blocks, without the need for a protecting group strategy or metal catalysts. The reaction is conveniently conducted at, or below, room temperature. The preparation of methyl-H-phosphinate esters is particularly interesting as it avoids the heretofore more common use of methyldichlorophosphine MePCl2.

Direct monoalkylation of alkyl phosphinates to access H-phosphinic acid esters

Simple alkyl phosphinates prepared by the silicate esterification method can be alkylated under Barbier-like conditions with butyl lithium at -78 °C followed by warming to room temperature. The method is limited to the more reactive electrophile such as allylic bromides and alkyl iodides. With these electrophiles good yields of H-phosphinic acid esters are generally obtained in a straightforward manner. Georg Thieme Verlag Stuttgart.

Recent advances in phosphorus-carbon bond formation: Synthesis of H-phosphinic acid derivatives from hypophosphorous compounds

This account summarizes the research conducted in our laboratory over the past five years. New methodologies were devised for the formation of P-C bonds with a focus on the reactions of hypophosphorous acid derivatives. Three types of reactions have been developed: palladium-catalyzed cross-coupling, room-temperature radical addition, and palladium-catalyzed addition. Our results are summarized in each of these areas and include some of our most recent data. (1) Our palladium-catalyzed cross-coupling has been extended to the direct coupling of alkyl phosphinates with a variety of aryl, heteroaryl, and even alkenyl electrophiles. (2) The addition of sodium hypophosphite under radical conditions is extended from alkenes to alkynes. (3) The catalytic addition of hypophosphorous compounds using palladium catalysts (hydrophosphinylation) is also discussed.

Phosphinic acid analogues of GABA. 2. Selective, orally active GABA(B) antagonists

In 1987, 25 years after the synthesis of the potent and selective GABA(B) agonist baclofen (1), Kerr et al. described the first GABA(B) antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABA(B) antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABA(B) antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABA(B) receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABA(B) antagonists interacted also with postsynaptic GABA(B) receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABA(B) antagonists showed also protective effects in various animal models of absence epilepsy.

Certain N-substituted-amino-alkane phosphinic acid derivatives having anti-epileptic properties

Compounds having GABAB -antagonistic properties, for example those of formula I STR1 wherein one of the radicals R1, R2 and R3 is hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical, another is hydrogen or, in the case of R1 or R2, hydroxy or, in the case of R1, halogen or, in the case of R2 together with R2 ', oxo, and the remaining radical is hydrogen, R1 ' is hydrogen or halogen, R2 ' is hydrogen, hydroxy or, together with R2, is oxo, R4 and R5 are hydrogen or R4 is an araliphatic or heteroarylaliphatic radical and R5 is hydrogen or an aliphatic radical, and R is an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, araliphatic, heteroarylaliphatic or aromatic radical having at least 2 carbon atoms or, when R1 is hydrogen or hydroxy, R2 is an aromatic radical and R1 ', R2 ' and R3 are hydrogen, R is methyl, and their pharmaceutically acceptable salts, can be used as active ingredients in medicaments for the treatment of epilepsies of the "petit mal" type. The invention relates also to novel compounds of formula I and processes for the preparation thereof.