Methylation Trimethyloxonium tetrafluoroborate

Cleavage of the chiral auxiliary is effected in a three-step procedure commencing with quatemization of the nitrogen with methyl fluorosulfonate, methyl trlfluoromethanesulfonate, or trimethyloxonium tetrafluoroborate. Reduction of the corresponding iminium salt 19 with NaBH4 and acidic hydrolysis of the resulting product affords substituted aldehyde 5 without epimerization of either stereocenter. 

The diquaternary salt 21 of 1,2,4-thiadiazole 1 is obtained when trimethyloxonium tetrafluoroborate is used as the methylating agent (Equation 4) <1972JOC2259>. 

Perhaps the most effective synthesis, albeit an expensive one, involves the direct methylation of alkylimidazoles using trimethyloxonium tetrafluoroborate with concomitant formation of the tetrafluoroborate anion as shown in Scheme 4.3 [12]. This is a single step reaction in which no chloride is present at any stage of the synthesis. The only by-product from this reaction is dimethyl ether which is a volatile and inert gas and it is easily removed. 

The vinylketene complex 140.g was shown to react toward electrophiles at the ketene oxygen. Although iodomethane had no effect, reaction with trimethyloxonium tetrafluoroborate caused methylation to produce the cationic complex 143 in fair yield. 

Methylation of pyrido[l,2-6]cinnolinium-ll-olate (17, R = H) with the soft dimethyl sulfate gave only the A -methyl derivative 43 (74JHC125), whereas the harder trimethyloxonium tetrafluoroborate yielded the 11-methoxy derivative 77 (92CB929). Methylation of pyrido[2,l-a]phthal-azinium-7-olate (20) with methyl iodide afforded a 1 9 mixture of the... 

Methylation of 5-amino-1,2,4-thiadiazoles (17) (R = H, Ph) leads to N-4 derivatives (18) (Equation (3)) <84CHEC-I(6)463>. The diquaternary salt (19> of 1,2,4-thiadiazole (1) is obtained when trimethyloxonium tetrafluoroborate is used as the methylating agent (Equation (4)) <72JOC2259>. 

The 1,3,4-thiazaphospholes are colorless, yellow, or red crystalline solids <85AG125> the 2-phenyl derivative is a pale yellow liquid. They are not oxidized by atmospheric oxygen or sulfur <86PS(28)7i>. Dimethyl sulfate or trimethyloxonium tetrafluoroborate methylates the nitrogen atom <85AG125,... 

Product elucidation of trimethyloxonium tetrafluoroborate and methyl iodide reactions with [l,2,3]triazolo[4,5- -pyridazines (Schemes 1-3) using mainly 2-D heteronuclear multiple bond correlation (HMBC). NMR... 

The unsymmetrical 3,6-dialkoxy-2,5-dihydropyrazines are prepared via the jV-carboxyanhy-drides of the particular amino acid (e.g., 7) and subsequent reaction with the methyl ester of glycine or alanine to give the corresponding cyclodipeptides (e.g., 8). These hexahydrodioxopy-razines are converted to the 2,5-dialkoxy-3,6-dihydropyrazines by alkylation using Meerwein salts, such as trimethyloxonium tetrafluoroborate or triethyloxonium tetrafluoroborate n lb. 

The block copolymer of ethylene oxide and 3,3-dimethylthietane shows useful properties of complexing halogen and heavy metal salts (79MI51402). Thietanes can be polymerized with methylmagnesium iodide as well as with a variety of electrophiles such as methyl sulfate, trimethyloxonium tetrafluoroborate, triethylaluminum, boron trifluoride and phosphorus trifluoride (67IC1461, 67MI51400). Thietane (210) has been patented as a stabilizer for poly(vinyl chloride) (73USP3767615). 

Decarboxylation of 117 was effected by treatment of 117 with LiCl in hot, aqueous HMPA at 105 °C providing 118 as a mixture of diastereomers that were separated and carried forward individually. Protection of the secondary amide group as the corresponding methyl lactim ether was accomplished by treating 118 with trimethyloxonium tetrafluoroborate in dichloromethane that contained cesium carbonate. Next, the indole nitrogen atom was protected as the corresponding Boc derivative by treatment with dicarbonic acid bis(rm-butyl)ester in the presence of DMAP and the silyl ether was removed with tetrabutylammonium fluoride to provide diol 119 in 52-78% overall yield from 118. Selective conversion of the allylic alcohol to the corresponding... 

O-Methylation of N-methylated derivatives under basic conditions is disappointing, 5063 but improved results are obtained using trimethyloxonium tetrafluoroborate (Scheme 13), or boron trifluoride-diethyl ether complex with diazomethane. 671 Conversely, methylation of the proline derived P-hydroxy acid using sodium hydride and iodomethane, as well as using trimethyloxonium tetrafluoroborate, gives the dolaproine unit (8) of dolastatin 10 in good yield. 68,691... 

Cerium(IV) ammonium nitrate, 67 Methylation (see also Alkylation) Dimethyl sulfate, 239 Trimethyloxonium tetrafluoroborate, 327 Methylenation of carbonyl groups... 

The 2-substituted tetrazole 1-oxides 550 were prepared from the corresponding hydroxytetrazoles 549 by methylation with trimethyloxonium tetrafluoroborate in CH2C12 at 20°C (1984BAU142) or by benzoylation of 1-hydroxytetrazole 549 (1913G71) (Scheme 165). Since N-alkylation and... 

The synthesis of pazopanib (1) involves sequential animation of 2,4-dichloropyrimidine 25 with 6-amino-2,3-dimethylindazole 24 and 5-amino-2-methyl-benzenesulfonamide 28. The 6-amino-2,3-dimethylindazole 24, on the other hand, was prepared from 2-ethylphenylamine 20 via 5-nitration with fuming nitric acid and concentrated sulfuric acid, followed by treatment with isoamyl nitrite and acetic acid to produce 6-nitro-3-methylindazole 22. The 6-nitro group was reduced with stannous chloride and concentrated HC1 in glyme and subsequently methylated at the C2 position of the indazole ring with trimethyloxonium tetrafluoroborate in acetone to produce 6-amino-2,3-dimethylindazole 24. The resultant indazole 24 was condensed with 2,4-dichloropyrimidine 25 in the presence of sodium bicarbonate in ethanol/THF and subsequent iV-methylation with iodomethane and cesium carbonate to produce 27. The 2-chloro group of pyrimidine was then allowed to react with 5-amino-2-methyl-benzenesulfonamide 28 in catalytic HCl/isopropanol and heated to reflux to deliver pazopanib hydrochloride (1) in good yield. 

Quaternization of compound (185) at N-5 by trimethyloxonium tetrafluoroborate increases reactivity to a large extent allowing displacement of the chlorine atom by 0-, S-, N-, and C-nucleophiles in the 6-position (193)-(196) under mild conditions (Scheme 31) <86HCA704>. 3-Methyl- and 1,3-dimethyl-4-thiolumazines (197) also show easy substitutions of the thioxo function. Ammonia... 

Base-sensitive substrates require some special precautions With the very potent alkylating agent methyl triflate, the highly hindered (and expensive) base 2,6-di-fert-butylpyridine can be used as shown in Scheme 4.114 22 205 Alternatively O-methylation using a combination of trimethyloxonium tetrafluoroborate and l,8-bis(dimethylamino)naphthalene in dichloromethane can be used although this is also a very expensive method [Scheme 4 115].206 Evans and co-workers have made a systematic study of the best conditions for 0-methylating hindered multifunctional substrates,207... 

Methyl (E)-4,S-alkadienoates. -Alkenyl- -butyrolactones react with allyltrime-thylsilanes in the presence of trimethyloxonium tetrafluoroborate to afford methyl (E)-4,8-alkadienoates in 75-100% yield (equation 1). 

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