Difluoro acetic

An intramolecular reductive addition of a,a-difluoro acetal radicals to olefins in a 5-exo-trig mode has been reported [95TL3531]. The reaction with the corresponding a-bromo-a,a-difluoroacetates gave no cyclized products. This method provides ready access to a,a-difluoro-y-lactones 34 in good yields. 

Abramov nucleophilic addition of various phosphorus acid esters to nucleoside aldehyde derivatives yielded the phosphonate-based iso-polar, non-iso-steric 5 -nucleotide analogues (28) containing a geminal hydroxy phosphonate moiety on the 5 -carbon of the pentofuranose ring. The enantiomerically pure D- and l- 2, 3, 5 -trideoxy-4 -[(ethoxyphosphoryl) difluoromethyl] thymidine analogues(29) have been synthesized from (i 5)-( )-2-methyl-5-(4-methyl-phenyl-sulfinyl)pent-2-ene and ethyl 2-(diethoxyphosphoryl)-2,2-difluoro-acetate in 45% overall yield over seven steps. ... 

The use of trichloro-, trifluoro-, or difluoro-acetic acids in conjunction with phosphorus oxychloride similarly alfords tri(or di)halogenomethyl-1,3,4-thiadiazoles (130)—(132). However, the condensation of chloroacetyl chloride with thiosemicarbazide did not yield the expected heterocyclic product, but gave merely l,l-bis(chloroacetyl)thiosemicarbazide, (ClCHaCO)2NNHCSNH2. ... 

A group of Russian workers [22 to 27] reported on the fluorination of mixtures of solid amines, amides, or cyano compounds with KF or CaF2. The reactions were carried out in a stream of F2 diluted with N2 at about -10 to +10°C. NF3 was one of the main products and was accompanied by fluorinated fragments of the compounds treated. The N-containing compounds studied include aliphatic amine hydrochlorides [22, 23], the amides of trifluoro- and difluoro acetic acid [24], potassium cyanate [25], silver and potassium thiocyanate [26], and a acetonitrile boron trifluoride complex [27]. 

C4H6F2O2 difluoro-acetic acid ethyl ester 454-31-9... 

Direct fluorination of propionyl fluoride and acetic anhydride has failed to yield the corresponding fluorocarbon derivatives the former sub strate gave a complex mixture of fluorinated propionyl fluorides, and hy drolysis of the product from the latter yielded a mixture of monofluM o and difluoro-acetic acids. 

In contrast to the wide application that nitrosyi chloride has found in terpene chemistry, nitrosyi fluoride has only recently been discovered. Its first use in steroid chemistry was reported by Boswell who treated cholesterol acetate with nitrosyi fluoride at 0° in methylene dichloride and obtained the 5a-fluoro-6-nitrimine (31) already mentioned in section VI (page 461) in connection with the synthesis of 6,6-difluoro steroids. This... 

R = H, R =Br, R" =Et) was prepared by cyclization of aroylacetate 314 (R = H, R =Br, r2 = H, X = F) (OOMIPIO). 9,10-Difluoro-3(5)-methyl-7-oxo-7//-pyrido[l,2,3- /e]-l,4-benzoxazine-6-carboxylic acid and its racemic form were prepared in the reaction of ethyl 2-(2,3,4,5-tetrafluorobenzoyl)-2-ethoxymethyleneacetate and (R)- or (i ,5)-2-aminopropanol and subsequent hydrolysis of the ring closed tricyclic esters (98MI45). Cyclization of ethyl 2-(2,3-difluoro-5-iodobenzoyl)-2-[A-(2-hydroxyethyl)aminomethylene]acetate 315 in the presence of K2CO3 in DMF at 95 °C for 3.5 h yielded 9-iodo-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- /e]-l,4-benzoxazine-6-carboxylate (01MIP2). 

The combined extracts were washed with water, dried over anhydrous sodium sulfate and concentrated to approximately 35 ml. The solution was chromatographed over 130 g of Florisil anhydrous magnesium silicate. The column was developed with 260 ml portions of hexanes (Skellysolve B) containing increasing proportions of acetone. There was thus eluted 6a,9a-difluoro-11/3,17a,21 -trihydroxy-16a-methy 1-1,4-pregnadiene-3,20-dione-21 -acetate which was freed of solvent by evaporation of the eluate fractions. 

After further working up there is obtained an oily crystalline residue which is subjected to chromatography on silica gel. The 16a-methyl-6a,9a-difluoro-A -pregnadien-11/3,21-diol-3,20-dione is eluated with ethyl acetatereacted with valeric acid chloride to give the valerate ester. 

A mixture of 290 mg of the 16,21-diacetate of 6a,9a-difluoro-16o --hYdroxY-hYdrocortisone, 30 cc of t-butanol, 0.5 cc of pyridine and 150 mg of selenium dioxide was refluxed for 53 hours under an atmosphere of nitrogen and cooled ethyl acetate was added and filtered through celite the solvent was evaporated to dryness under reduced pressure, the residue... 

Diethyl Ar,Af-dimethylaminomethylenemalonate was reacted with 7,8-difluoro-3-methyl-l,4-benzoxazine in acetic acid at 80-90°C for 5 hr to give (l,4-benzoxazin-4-yl)methylenemalonate (272) in 74.8% yield [86JAP(K)246172, 86J AP( K)246188]. 

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