Diethyl difluoro

Diethyl malonatc13 gives four products upon reaction with perchloryl fluoride diethyl difluoro-malonate, diethyl ethylmalonate, diethyl ethylfluoromalonate and diethyl fluoromalonate the product distribution depends on the reaction conditions. A number of esters are fluo-rinated,14 15 while (pentafluorophenyl)acetonitrile is converted into mono- and disubstituted products in the presence of cesium fluoride.16... 

Propenamide N.N-Diethyl Difluoro-2-trifluoromethyl- ElOb,. 436 (Educt) EI0b2. 112/353 (- HF -> En)... 

Diethyl difluoro(trimethylsilyl)methylphosphonatc (42) with arenecarbaldehydes and aryl methyl ketones in the presence of cesium fluoride gives alkylphosphoric acid derivatives. ... 

The addition of diethyl 1-bromo-l,1-difluoromethylphosphonate to various electron-deficient alkenes initiated by a cobaloxime(III)/Zn bimetallic system gives the corresponding diethyl difluoro-alkylphosphonates (1 1 Michael-type adducts) in moderate to good yields (34-72%). Cyclic a,p-unsaturated ketones and electron-rich alkenes produce somewhat lower yields of addition products (18-58%), along with small quantities of diethyl difluoromethylphosphonate. A radical mechanism has been proposed for this process. ... 

A synthesis of racemic fmoc-protected 4-phosphonomethylphenylalanine starts with the Arbuzov preparation of (257) (R = Me or Bu ) standard modifications to the aryl methyl group lead to the desired (258). Two procedures have been adopted for the preparation of the N-ivaoc or iV-boc derivatives of the difluoro derivative (259). In the first, triethyl phosphite and 4-(bromomethyl)benzoyl bromide and treatment of the resultant aroyl phosphonate with the DAST reagent yields (262) this reacts with the carbanion from (263) to give (264) hydrogenation of which (with PdCla) affords (260), then converted into its N-fmoc derivative and de-esterified with MeaSil. In the second procedure, triethyl phosphite and 4-iodobenzoyl chloride, followed by DAST reagent, yielded diethyl [difluoro(4-iodophenyl)methyl]phosphonate which was caused to react... 

Fluorodesilylation is a valuable alternate method for the in situ generation of carbanions, which can be trapped as hydroxy[ C]methyl derivatives through treatment with H CHO. This sequence, applied to diethyl difluoro(trimethylsilyl)methylphospho-nate (127), afforded the 0-silylated intermediate 128. which served as a precursor for the preparation of 2,2-difluoro[l- C]ethylene. This was conveniently accomplished through thermolysis of 128 in the presence of catalytic amounts of CsF °. 

S)-[(7,8-difluoro-2,3-dihydro-3-methyl-4 -l,4-benzox-azin-4>yl)methylene]propanedioic acid diethyl ester... 

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]. 

Diethyl (7,8-difluoro-3-methyl-3,4-dihydro-2//-benzoxazin-4-yl)methy-lenemalonate was cyclized in boiling acetic anhydride on the action of boron trifluoride in THF to give a pyrido[l,2,3-de]-l,4-benzoxazine-6-... 

Indolylmethylenemalonate (1484) was obtained in 92% yield from N-[3,4- difluoro - 2 - ( 2 - hydroxypropyl phenyl ] aminomethylenemalonate (1483) by the action of a mixture of triphenylphosphine and diethyl azodi-carboxylate in THF at —20°C (88JHC1567). 

More conclusive evidence for the intermediacy of benzocyclopropenyl cations was obtained upon chloride/fluoride exchange of 22 with AgF in acetonitrile, which led to the chloro-fluoro derivative 278 and, ultimately, to the difluoro compound 279 in almost quantitative yield. Reaction of 22 with LiAlH AlClj afforded 2,5-diphenylbenzocyclopropene (264), while that with ethyl magnesium bromide lead to the diethyl derivative 280. Phenylmagnesium bromide and methylmagne-... 

Diethyl (i S)-2-[(4i )-3-(ferf-Butoxycarbonyl)-2,2-dimethyloxazolidin-4-yl]-l,l-difluoro-2-hydroxy-ethvlphosphonatef109 ... 

A soln of 1.4 M BuLi in hexane (6.79 mL, 9.51 mmol) was added dropwise by syringe to a stirred soln of the diethyl (f S)-2-[(4f )-3-(tert-butoxycarbonyl)-2,2-dimethyloxazolidin-4-yl]-l,l-difluoro-2-hydroxy-ethylphosphonate (3.96 g, 9.51 mmol) in dry THF (50 mL) at —78 °C followed immediately by the addition of phenyl chlorothionoformate (1.97 mL, 14.3 mmol). After 15 min at —78 °C, a soln of NaHC03 (25 mL) was added and extracted with Et20 (4x 5mL). The combined organic extracts were dried (MgS04), filtered, and the solvent removed under reduced pressure. The residue was purified by flash chromatography (silica gel, EtOAc/hexane 10 90 to 30 70) to give the pure product yield 4.05 g (79%). 

Hiyama and coworkers produced the same allylation compounds via the in situ reaction of l,l-difluoro-3-(dimethylphenylsilyl)propene and aldehydes with catalytic tris(diethyl-aminojsulfonium difluorotrimethylsilicate (TASF) or potassium f-butoxide (equation 85)78-79. 

Diethyl(trifluoromethyl)amine and [Difluoro(phenyl)methyl)(dimethyl)ainine... 

Diethyl(trifluoromethyl)amine (19) and [difluoro(phenyl)methyl](dimethyl)amine (21) are synthesized from the corresponding diethylformamide (18) and N, /V-dimethylbenzamide (20), respectively. The fluorination is achieved with sulfur tetrafluoride in the presence of potassium fluoride at 150l,C.36... 

Diethyl(trifluoromethyl)amine (19 14.1 g, 0.1 mol) was added dropwise to i-PrOH (22 6g, 0.1 mol) at 40CC with stirring, an exothermic reaction occurred and the mixture was brought to reflux. Once the addition was complete the mixture was stirred for a further 15 min. The volatile 2-fluoropropane (23) which evolved during the course of the reaction was condensed into a cold trap at — 78°C yield 4.6 g (74%). An identical yield was obtained when the same procedure was performed with [difluoro(phenyl)-methyl](dimethyl)amine (21) instead of 19. 

Apparently chlorine and trifluoromethanesulfonate groups attached to boron and silicon can be replaced by fluorine in lithium fluoride at lower temperatures than that reported for C-X (X = halogen) exchange. Dichloroborane 5 is converted to the difluoro derivative 6 with lithium fluoride in diethyl ether at 0-22°C.7... 

Silicon trifluoromethanesulfonate 9 react with lithium fluoride even at — 30°C in diethyl ether to afford the difluoro compound 10 in 63% yield.9... 

Phosphonate Diethyl Bromo-difluoro-methane ElOb,. 671 f-[CBr2F2 + (RO)3P]... 

Phosphonate Diethyl 2-Chloro-2,2-difluoro-1 -hydroxy-1 -methyl-ethane ElOb. 681 [F2CIO-CO-R + H-PO(RO)2]... 

Butandioate Diethyl 2,3-Difluoro-E10b,.316f.(En 4 F,) E10b,.96 (Educt)... 

Malondioate Diethyl (Bromo-difluoro-methyl)-melhyl- ElOa, 558 (Br -> CR R )... 

Phosphonate Diethyl 1-Diethoxy-phosphoryloxy-2,2-difluoro-ctheneEI0b2,376[-CIF -> Kctcn CO + P(OR)3]... 

Phosphonate Diethyl 1.1-Difluoro-2-hydroxy-2-(4-pyridyl)-ethanc ElOb, 418 (Het-CHO + R3Si-CF2- )... 

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