Preparation of difluorophosphonoacetic acid and its derivatives

Synthesis of α-fluorinated phosphonoacetate derivatives using electrophilic fluorine reagents: Perchloryl fluoride versus 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor®)

“…Thus, inclusion of an additional silylation step using iodotrimethylsilane to convert the ethyl P,P-bis(trimethylsilyl) esters [2,17] into tris(trimethylsilyl) esters or preliminary basic hydrolysis of the C-O ester can be avoided [5]. The acids are hygroscopic but are easily converted to stable (>1 year), crystalline bis(dicyclohexylammonium) or pyridinium salts.…”

“…A similar route to 3a via generation of an organozinc reagent from (EtO) 2 P(O)CF 2 Br followed by CuBr-catalyzed reaction with ethyl chloroformate has been described [17]. P,P-diethyl difluorophosphonoacetic acid (3d) was prepared by CO 2 -carboxylation of lithium diethyl difluoromethylphosphonate [5].…”

Synthesis and some heterocyclization reactions of new diethyl (1,1-difluoro-3,3-dicyano-2-trifluoromethylallyl)phosphonate and ethyl 3,3-dicyano-2-[(diethoxyphosphoryl)difluoromethyl]acrylate

“…The J values are given in Hz and chemical shifts (d) in ppm. Ethyl 3-(diethoxyphosphoryl)-3,3-difluoro-2-oxopropionate (2) was prepared as previously described [10]. Known synthetic strategies were applied to obtain diethoxyphosphoryl pentafluoroacetone (1) [12] and diethyl bromodifluoromethylphosphonate [16].…”

“…General procedure for preparation of [(6-amino-5-cyano-3-methyl-1-aryl-4-trifluoromethyl-4,7-dihydro-1H-pyrazolo [3,4-b]pyridin-4-yl)-difluoromethyl]-phosphonic acid diethyl esters (10) Alkene 4 (0.2 g, 0.6 mmol) was added with stirring to a solution of the corresponding aminopyrazole (0.6 mmol) in 15 ml of abs. CH 3 CN, the mixture was kept at RT for 24 h and solvent was evaporated.…”

“…Recently, we have prepared CF 2 H-and CF 2 Cl-containing dicyanoethylenes and studied them as precursors of heterocycles [1]; also, syntheses of new heterocyclic compounds modified with difluoromethylphosphonate group have been initiated in connection with a search for biologically active phosphates stable to hydrolysis and phosphorylase action [9]. From ethyl 3-(diethoxyphosphoryl)-3,3-difluoro-2-oxopropionate 2 [10] we obtained derivatives of quinoxaline, indole, and imidazole substituted with the (EtO) 2 P(O)CF 2 group in one simple stage [11]. This work continues development of the synthesis of heterocyclic compounds modified with difluoromethylphosphonate group using new precursors of heterocycles, i.e.…”