L- -2,2,2-trifluoroethyl

CN 7-chloro-5-(2-fluorophenyl)-l,3-dihydro-l-(2,2,2-trifluoroethyl)-27/-l,4-benzodiazepine-2-thione... 

Organic-soluble lanthanide chelates have been used to probe lipophillic systems. The compound 4-(4-dipentylamino-( )- S-styryl)-l-(2,2,2-trifluoroethyl)pyridinium perchlorate (22) was employed as a probe in dimyristoylphosphatidylcholine vesicles. Probe molecules assembled in the inner and outer shells of the vesicle as evidenced by the presence of two signals in the NMR spectrum (376 MHz). Even though addition of Eu(fod)3 promoted vesicle fusion, only one of the signals shifted. The shifted signal was likely from the probe molecule on the outer shell, as the internal P signal of the phospholipid did not shift in the presence of Eu(fod)3 ". 

CN 6-chloro-3,4-dihydro-3-[((2,2,2-trifluoroethyl)thio]methyl]-2H-l,2,4-benzothiadiazinc-7-sulfonamide... 

Trifluoroethyl)-l,3-dioxino[5,4-/]quinoline-9-carboxylic acid (834) was obtained by the cyclization of N-(2,2,2-trifluoroethyl)-N-(l,3-benzodioxan-6-yl)aminomethylenemalonate (833) in boiling phosphoryl chloride [77JAP(K) 142098]. 

The ring closure of A-(2,2,2-trifluoroethyl)-N-[2-(l-piperazinyl)-4-pyrimidinyl]aminomethylenemalonate (1048) in polyphosphoric acid at 200-220°C for 10 min yielded 8-trifiuoroethylpyrido[2,3- /]pyrimidine-6-carboxylic acid (1049) [77JAP( K) 139094]. 

Kutsuna, S., Chen, L., Ohno, K., Tokuhashi, K., and Sekiya, A. Henry s law constants and hydrolysis rate constants of 2,2,2-trifluoroethyl acetate and methyl trifluoroacetate, Atmos. Environ., 38(5) 725-732, 2004. 

Racemization of (S)-l-phenylethanol in the presence of an Ru p-cymerie binu-clear complex and triethylamine was much faster in [BMIm][BF4] or [BMIm][PF,s] than in toluene [136]. A range of chiral alcohols (Figure 10.17) were resolved in the presence of this complex and immobilized PsL. The reactions were performed in [BM Im][PF6] with the activated ester 2,2,2-trifluoroethyl acetate as the acyl donor (Figure 10.17). A hydrogen donor was required to prevent the formation of partially oxidized byproducts. Enantiomerically pure acetates were isolated in high yield (>85%). 

A large number of fluorinations of partially fluorinated ethers have been successfully carried out. A few examples are fluorination of methyl 2,2,2-trifluoroethyl ether (12),85 1,1,2,2-tetrafluoroethyl 2,2,2-trifluoroethyl ether (13),85 2-(l,l,2,3,3,3-hexafluoropropyl)tetrahydro-furan (14),86 difluoromethyl 2,2,2-trifluoroethyl ether (15),10 and bis(2,2,2-trifluoroethyl) ether (16).10 Manganese(III) fluoride is more reactive than cobalt(III) fluoride in the last two fluorinations. 

C) Preparation of 2-Methyl-3-(2,2,2-Trifluoroethyl)Thiomethyl-6-Chloro-7-Sulfamyl-3,4-Dihydro-l,2,4-Benzothiadiazine-l,1-Dioxide To 4.6 g (0.015 mol) of 4-amino-2-chloro5-(methylsulfamyl)benzenesulfonamide in 30 ml of the dimethyl ether of ethylene glycol is added 4.08 g (0.02 mol) of 2,2,2-trifluoroethylmercaptoacetaldehyde dimethylacetal followed by 1 ml of ethyl acetate saturated with hydrogen chloride gas. The resulting solution is refluxed for 1.5 hours, cooled and then slowly added to cold water dropwise with stirring. The crude product is filtered, dried and recrystallized from isopropanol (3.2 g), MP 202° to 202.5°C. A second recrystallization from isopropanol raised the MP to 202° to 203°C. 

In a similar context, 6-18F-3,4-dihydroxyphenylalanine (6-18F-DOPA) was synthesized by direct fluorination of L-3-(3-hydroxy-4-pivaloxyphenyl)alanine (ra-P-DOPA) with Ac018F in acetic acid resulting in the 2- and 5-18F isomers. Hydrolysis of the reaction mixture in hydrochloric acid followed by HPLC separation gave 6-18F-DOPA (equation 23)44. Another application of Ac018F was reported in the synthesis of a trimethyl tin precursor of 2-oxoquazepam, 7-chloro-1 -(2,2,2-trifluoroethyl)-1,3--dihydro-5-(2-fluorophenyl)-2//-l,4-benzodiazepin-2-one, a benzodiazepine agonist, and its conversion to [18F]-2-oxoquazepam by reaction with AcQ18F (equation 24)45. 

Merck process research group developed a short and efficient synthesis of 3-(2,2,2-trifluoroethyl)-hexahydro-2//-l,4-diazepin-2-one 85 as part of an ongoing research program to identify peptidase inhibitors <07S2779>. 

To bis(2,2,2-trifluoroethyl) ethyl 2-phosphopropinate (3.75 mmol), 18-crown-6 (10.18 mmol) in 30 ml of THE at -42 °C was added solid KHMDS (3.68 mmol). The solution was cooled to -78 °C, butyraldehyde (2.5 mmol) added dropwise, and the mixture stirred 8 hours at -78 °C and 12 hours at -20 °C. The mixture was re-cooled to -78 °C, l.OM LiBEtjH (10.0 mmol) in THF added, the reaction warned to 25°C over 4 hours, and stirred an additional 10 hours. The reaction was quenched with EtOAc and poured over distilled water. The mixture was purified chromatography on silica gel with CH2Cl2/EtOAc, 97 3, and the product isolated as an oil in 90% yield. 

Applying Danheiser s method (96JOC134), phenyldiazenyl ketone 67 reacts with lithium bis(trimethylsilyl)amide in absolute tetrahydrofuran followed by 2,2,2-trifluoroethyl triflate forming a mixture of C- and O-triflate intermediates 68 and 69, respectively. Upon treatment with mesyl azide, the mixture of 68 and 69 provides the desired l-diazo-4-methyl-4-[(E)-phenyldiazenyl]pentan-2-one (58) as yellow crystals in very good yield (87%) (Scheme 16). 

Trifluoroethyl 2-(trifluoromethyI)prop-2-enoate reacts with various dienes to provide cycloadducts in high yields. A typical example is the reaction with ( )-l-methoxy-2-methyl-3-(trimethylsiloxy)buta-l,3-diene leading to the trifluoromethyl-substituted cyclohexenone 13 which was used as a precursor of 16,16,16-trifluororetinal." The reaction has also been performed with a chiral dienophile."... 

To a solution of ( )-1-methoxy-2-methyl-3-(trimethylsiloxy)buta-l,3-diene (lOg, 54mmol) in CIljClj (25 mL) was added a solution of 2,2.2-trifluoroethyl 2-(trifluoromethyl)acrylate (11.8g, 54mmol) in CH2CI2 (15mL) at 0 C under argon, and the solution was stirred for 3 min. After evaporation of the solvent, MeOH (30 mL) and TsOH (2 g, 10.5 mmol) were added at 0 C. The resulting solution was stirred at the same temperature for 1.5 h. F.vaporation of the solvent and vacuum distillation of the residue gave 13 yield 16.5 g (87%) bp 88 C/3 Torr. 

Trifluoroethyl 3-Methyl-4-oxo-l-(trifluoromethyl)cyclohex-2-ene-l-carboxylate (13) Typical Procedure 1 1... 

PFsNOSiQH, Phosphinimidic acid, P,P-dimethyl-iV-(trimethylsilyl)-2,2,2-trifluoroethyl ester, 25 71 PF6lrCigH22, Phosphate(l-), hexafluoro-, ( n -l,5-cycIooctadiene)bis(pyridine)-iridium(l), 24 174... 

TV.7V-Dimethylbenzylamine [64,65], 2,4.6-tris(dialkylamino)-l,3,5-triazines [66], N-(2,2,2-trifluoroethyl)amines [67,68], and TV-(2,2-difluoroethyl)amines [68] exhibit similar behavior. Methoxylation of enamines results in substitution at both the vinylic and the allylic positions [61]. 

The potassium salt of /2z 5(2,2,2-trifluoroethyl) 1-(methoxycarbonyl)methylphosphonate is alkylated with homogeranyl iodide in THF-HMPA in the presence of 18-crown-6 (1 eq). The use of Et2O or toluene at reflux- gives less satisfactory results. Treatment of diethyl 1-(ethoxycarbo-nyl)methylphosphonate with [ C]methyl iodide and allyl bromide" using EtONa in absolute EtOH produces diethyl l-[ - C]methyl and l-allyl-l-(ethoxycarbonyl)methylphosphonates in good yields. The tandem Michael addition-alkylation of l-(ethoxycarbonyl)vinylphosphonate has been reported with methyl cuprate, but the alkylation is complete only in the presence of Lewis bases like HMPA or TMl. "... 

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