Ethyl 2,2-difluoro-2-

Difluoroserine is unstable, but some O- and A -protected derivatives of ethyl difluoro-serinate have been prepared. As for trifluoroalanine, a good precursor is ethyl trifluoro-pyruvate. Synthesis is based on the addition of an alcohol on gem-difluoroenamine, resulting from the reductive cleavage of a C—F bond of an imine of ethyl trifluoro-pyruvate (cf. Chapter 2) (Figure 5.10). ... 

Reduction of a S-aminoketone resulting from the addition of an equivalent of a glycinate anion on ethyl difluoro- or trifluoroacetate is stereoselective and leads to ethyl di- or trifluorothreoninate threo (syn). Release of the acid, performed by saponification, is accompanied by a partial epimerization into an alio compound. However, the amino acids are obtained in enantiopure forms by using a lipase. . It s important to note that (25, 35)-difluorothreonine exhibits activity toward the growth of leukemia cell hnes comparable to 5-fluorouracil. ... 

Ethanoate Ethyl Difluoro-fluoro-sulfonyl- ElOa. 373 (Educt)... 

Acrylate Ethyl Difluoro-2-trifluoi O-nicthyl- E10b2, I5f. (Educt). 353/357 ( — HF -> En)... 

Phosphorane Bis-[pennifluoro-ethyl]-difluoro-(2-pentafluoroethoxy-tcti ufluoro-elhyl)- ElOa. 197 (19H - 19F/P - PF2)... 

Ethanoate Ethyl Difluoro-phenyl-ElOa, 415 (CO -> CF2) ElOb, 178 (CO -> CF,)... 

Phosphorane Bis-[penlnfluoro-ethyl]-difluoro-(tritriacontafluoro-hexadexvl)- ElOa. 197 (43 H 43 F P -> PF,)... 

Bis-[pentafluoro-ethyl]-difluoro-EI0b2. 275f. (4,5-R F2-pyridazin/hv)... 

The systematic names are as follows (10) (R, S )-7-(3-(l-amiQoethyl)-l-pyrrohdinyl)l-ethyl-6-8-difluoro-l,4-dihydro-4-oxo-3-quiQolinecarboxylic acid ... 

Fig. 2. Preparation of precursors for closure to stmcture (24) at the a bond. (25) = 2,4-dichloro-5- uoroacetophenone [704-10-9], (26) = 4-bromo-2,5-difluoroacetophenone [123942-11 -0], (27) = 2,4-dichloro-5-fluoroben2oic acid [86522-89-6], (28) = 4-bromo-2,5-difluoroben2oic acid [28314-82-1] (29) = ethyl 3-(2,4-dichloro-5-fluorophenyl)-3-oxopropanoate(30) = ethyl 3-(2,5-difluoro-4-bromophenyl)-3-oxopropanoate...

Oxetane, 2-(o -chlorobenzyl)-2-phenyl-X-ray crystal structure, 7, 366 Oxetane, 3-chloromethyl-3-ethyl-ring strain, 7, 370-371 Oxetane, 2-(o-chlorophenyl)- H NMR, 7, 367 Oxetane, 2-cyano-synthesis, 7, 391-392 Oxetane, 2-cyano-3,3-dimethyl-2-phenyl-thermolysis, 7, 372 Oxetane, 2,2-dialkoxy-synthesis, 7, 396 Oxetane, 2,2-dialkyl-isomerization, 7, 377 Oxetane, 3,3-dialkyl-alkylative cleavage, 7, 381 polymers, 7, 382 Oxetane, 2-diethylamino-synthesis, 7, 390 Oxetane, 3,3-difluoro-molecular dimensions, 7, 365 Oxetane, 2,2-dimethyl-mass spectra, 7, 368-369 photolysis, 7, 373 synthesis, 7, 393 Oxetane, 2,3-dimethyl- H NMR, 7, 366 thermolysis, 7, 372 Oxetane, 2,4-dimethyl-mass spectrum, 7, 369... 

On treatment with DAST, keto esters undergo oxidative fluorination- ethyl acetoacetate and DAST in W-methylpyrrolidone give a 48-58% yield of a mixture of equal parts of ethyl cis- and trans-2,3-difluoro-2-butenoate [200] (equation 100)... 

Ethyl chlorodifluoroacetate has been used in a silicon-induced Reformatsky-Claisen reaction of allyl chlorodifluoroacetates in the presence ot zinc as a route to 2,2-difluoro unsaturated acids [( S] (equahon 58) When this methodology is applied to chlorodifluoropropargylic esters, the corresponding allenic esters are formed [SS]... 

An on-line chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI/MS/MS) methods was developed for rapid screen of pharmacokinetics of different drugs, including 5 (98RCM1216). The electron impact mass spectrum of 5 and ethyl 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7Ff-pyrido[l,2,3- fe]-l,4-benzoxazine-6-carboxylate was reported (97MI28). Electron impact/Fourier transform... 

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). 

Reaction of 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l, 2,3- e]-1,4-ben-zothiazine-6-carboxylic acid and its ethyl ester with B(OH)3 in AC2O in the presence of ZnCl2 afforded 6-[(diacetoxyboryl)oxycarbonyl] derivative 323 (R = OAc)], which was reacted with primary and cyclic amines to give 10-amino-9-fluoro-7-carboxylic acid derivatives 324 (97MI41, 98MI30). 6-[(Difluoroboryl)oxycarbonyl derivative 323 (R = F) was obtained from ethyl 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylate with BF3-THF complex. Reaction of 323 (R = F) and 1-methylpiperazine in DMF at 50-60 °C and subsequent acidic hydrolysis afforded 7 (97MI1). 

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... 

Diiluoro-2,l,3-benzoxadiazole 1-oxide and ethyl acetoacetate gave ethyl 6,7-difluoro-3-methyl-2-quinoxalinecarboxylate 1,4-dioxide (486) (neat... 

Ethyl 3-bromomethyl- (270, R = Br) gave ethyl 2-acetoxymethyl-6,7-difluoro-2-quinoxalinecarboxylate 1,4-dioxide (270, R = OAc) (AcOH-AcMe, 20°C, Et3N dropwise, 15 min then substratej, slowly, 20°C, 2h 80%). ° ... 

Ethyl 3-bromomethyl-6,7-difluoro-2-quinoxalinecarboxylate 1,4-dioxide (84) gave 6-fluoro-2-methyl-7-methylamino-2,3-dihydro-17/-pyrrolo[3,4-h]quinoxalm-l-one 4,9-dioxide (85) (MeCN, MeNH2i, 15°C, 90 min 87% note additional replacement of one fluoro substituent) analogs likewise. ° ... 

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