0-Methylations, trimethylsilyldiazomethane

The desilylacetylated qrcloadducts, produced from the reactions of trimethylsilyl-diazomethane with 3-crotonoyl-2-oxazolidinone or 3-crotonoyl-4,4-dimethyl-2-oxa-zolidinone, were transformed to methyl traws-l-acetyl-4-methyl-l-pyrazoline-5-car-boxylate through the reactions with dimethoxymagnesium at -20 °C. When the optical rotations and chiral HPLC data were compared between these two esters, it was found that these two products had opposite absolute stereochemistry (Scheme 7.39). The absolute configuration was identified on the basis of the X-ray-determined structure of the major diastereomer of cycloadduct derived from the reaction of trimethylsilyldiazomethane to (S)-3-crotonoyl-4-methyl-2-oxazolidi-none. 

Aryldiazomethane can also be used for iron porphyrin-catalyzed alkene cyclopropanation [55]. For example, the treatment of p-tolyldiazomethane with styrene in the presence of [Fe(TTP)] afforded the corresponding arylcyclopropapane in 79% yield with a high transicis ratio of 14 1 (eq. 1 in Scheme 11). Interestingly, when bulkier mesityldiazomethane was used as carbene source, ds-selectivity was observed (cisitrans = 2.0 1). Additionally, mesityldiazomethane was found to react with frans-p-styrene, the latter was found not to react with EDA or trimethyl-silyldiazomethane under the similar reaction conditions, to give l-mesityl-2-methyl-3-phenylcyclopropane in 35% yield. Trimethylsilyldiazomethane is also an active carbene source for [Fe(TTP)]-catalyzed cyclopropanation of styrene, affording l-phenyl-2-trimethylsilylcyclopropane in 89% yield with transicis ratio of 10 1 (eq. 2 in Scheme 11). 

Bispyribac-sodium is recovered as the free acid, bispyribac, from plant material and soil by acetonitrile-water (4 1, v/v) solvent extraction. After filtration, the acetoni-tirile is evaporated under reduced pressure. The aqueous residue is dissolved in buffer solution (pH 7.4) and washed with ethyl acetate to separate the impurities from the extract. Then the solution is acidified and extracted with ethyl acetate. The ethyl acetate is evaporated. The residue is methylated with trimethylsilyldiazomethane. 

Methylation of the residues of the ethyl acetate extract prepared in Section 6.2.1 should immediately be performed with trimethylsilyldiazomethane, because bispyribac is unstable under acidic conditions. 

Alkylating reagents such as boron trifluoride-methanol, sulfuric acid-methanol, methanol-hydrochloric acid and methyl iodine-sodium hydride do not react efficiently with pyrithiobac. Trimethylsilyldiazomethane may be used for the methyl-ation of pyrithiobac. 

The main drawback to this reaction is the toxicity of diazomethane and some of its precursors. Diazomethane is also potentially explosive. Trimethylsilyldia-zomethane is an alternative reagent,42 which is safer and frequently used in preparation of methyl esters from carboxylic acids.43 Trimethylsilyldiazomethane also O-methylates alcohols.44 The latter reactions occur in the presence of fluoroboric acid in dichloromethane. 

Initially, the oxidation conditions chosen for 154 to 157 were the modified ruthenium tetraoxide conditions of Sharpless and co-workers.44 The crude oxidation products were converted to methyl esters 106,160, 161, and 162 and their C-2 epimers 163 to 166 using either diazomethane or trimethylsilyldiazomethane.77 The epimer ratios were determined from integration of the H NMR spectra of the crude esterification products to ensure that accurate ratios were obtained without losing minor isomers during chromatography. The results obtained are summarized in Scheme 60 and Table 15. 

Benazepril, benazeprilat, and the corresponding deuterium-labelled internal standards (I.S.) were supplied by Novartis (Basle, Switzerland). All the chemicals were of analytical grade. Hexane and toluene (Pestipur SDS) were obtained from Solvants Documentation Synthese (Pepin, France). Methyl tert. -butyl ether and 2 mol/L trimethylsilyldiazomethane solution in hexane were purchased from Fluka (Saint-Quentin Fallavier, France). Hydrochloric acid (0.1 mol/L),... 

The use of trimethylsilyldiazomethane with methanol provides a less hazardous method for preparing methyl esters under mild conditions than ethereal diazomethane solution. Trimethylsilyldiazomethane is commercially available, obviating the need to synthesize diazomethane daily. It is a stable and safe substitute for either hazardous diazomethane or corrosive reagents containing boron trifluoride. 

Rimmer DA, Johnson PD, Brown RH (1996) Determination of phenoxy add herbicides in vegetation, utilising high-resolution gel permeation chromatographic clean-up and methylation with trimethylsilyldiazomethane prior gas chromatographic analysis with mass-selective detection. J Chromatogr A 755 245-250... 

The step 4 product (490 mg) dissolved in 8 ml methyl alcohol was treated portion-wise with 5 ml 2M trimethylsilyldiazomethane at ambient temperature. After the reaction was complete, it was quenched with glacial acetic acid and concentrated. The residue was purified by chromatography using CH2Cl2/methyl alcohol, 95 5, and 410 mg of product isolated as an oil. 

Starting from (+)-diethyl tartrate (2), bromobutenolide 18 was obtained in nine steps. Three of the four C=C double bonds were built up using a Wittig reaction (11—>12), an Ando- y Q Horner-Wadsworth-Emmons reaction (13— 15) and (3-elimination (16 18). From (-)-actinol (3) stannane 23 and sulfone 24 were synthesized in 9 and 13 steps, respectively. Their common intermediate, alkyne 22, was synthesized using methoxycarbonylation. Sharpless asymmetric epoxidation and Ci-elongation with lithio trimethylsilyldiazomethane. Stannane 23 was obtained upon hydrostannylation and TBS deprotection. Sulfone 24 was obtained after addition to methyl tetrolate, reduction, Mukaiyama redox condensation, acetylation and catalytic oxidation. 

CYCLOADDITIONS f-Butyicyanoketene. a-Chloro-N-cyclohexylpropanaldoxime. Chlorosulfonyl isocyanate. Dichloroke-tene. Dimethyl acetylenedicarboxylate. Diphenyl ketene, 2-Methoxyallyl bromide. 2-Methoxy-6-methyl-l,4,3,5-oxathiadia-zine 4,4-dioxide. Oxygen, singlet. 4-Phen-yl-l,2,4-triazoline-3,5-dione. Silver fluoro-borate. Trimethylsilyldiazomethane. 

A more thorough analysis of the enantioselectivity of several commercially available alkaline proteases was performed by determining the enantioselectivity fador E of these enzymes in the hydrolysis of (R,S)-4. In order to determine the enantioselectivity factor E accurately (the kinetic ratios for the conversion of the two enantiomers in a first-order kinetic resolution) [11], accurate measurement of the optical purity of the product acid and unreacted ester is necessary. Separation of the carboxylic acid enantiomers by gas chromatography was not possible due to decomposition of the acid on the column, so a derivatization method was developed to convert the acid into the corresponding methyl ester. Treatment of the extracted acid and ester with trimethylsilyldiazomethane resulted in the conversion of the acid into the methyl... 

Aliquots (200 pL) of the well stirred reaction mixture were removed periodically and added to a 2 mL vial containing 1.5 mL of MTBE. Hydrochloric acid (20 pL of 1 N) was added, the vial was shaken and then the solvent was dried over anhydrous MgS04 and the solution was transferred into a vial. Five drops of methanol and 1 drop of trimethylsilyldiazomethane solution (2 M in hexane) were added to convert the carboxylic acid product into the methyl ester for GC analysis. A J W Scientific Cyclodex B column (0.25 micron, 30 meterx0.25 mm) was used. GC conditions 110°C for 10 min then l°C/min for 5 min. Retention times (S)-methyl ester 8.35, (R)-methyl ester 8.65, (S)-ethyl ester 11.35, and the (R)-ethyl ester at 11.64 min. 

Trimethylsilyldiazomethane is a commercially available equivalent to diazomethane. It reliably converts an acid to the methyl ester. Methanol is an essential co-solvent for this esterification. 

Trimethylsilyldiazomethane, Mc3SiCHN2, is regarded as a stable and safe substitute for diazomethane [213]. It is believed that the expected product, RCOOCH2SiMe3, is formed first, but quickly converted to the methyl ester (with displacement of Me3SiCH20CH3) by methanol present in the reaction mixture. 

Miscellaneous Reactions. Trimethylsilyldiazomethane converts acid- and base-sensitive maleic anhydride derivatives into the corresponding bis(methyl esters) (eq 70). Terminal silyl enol ethers are conveniently prepared from aldehydes by first treating the carbonyl compound with TMSC(Li)N2, followed sequentially by methanol and Rh2(OAc)4 (eq 71). The method works well with base-sensitive substrates and is superior to the attempted regioselective deprotonation/O-silylation of the corresponding methyl ketone. ... 

An alternative reagent, trimethylsilyldiazomethane in hexane, is commercially available and appears useful for preparation of bile acid methyl esters [62], Like carboxylic acid groups, hydroxyl groups also require protection prior to GC-MS analysis. A common and mild method to prepare trimethylsilyl (TMS) ethers is to react the sample with a mixture of dry pyridine, hexamethyldisilazane (HMDS), and trimethylchlorosilane (TMCS), 3 2 1 or 9 3 1 (by volume) with, or without heating [32], However, if 0X0 groups are present in the bile acid, this reaction can yield enol-TMS ethers and multiple products. This artifact can be avoided by converting the 0X0 group into an oxime, usually a methyloxime (MO). To do this, the sample is dissolved in 50 pL pyridine with 5 mg methoxyammonium chloride and heated for 30 min at 60°C [32]. 

The preparations of inhibitors 128 and 130 were performed applying a divergent synthetic pathway (Scheme 27). First, the free radical hydrophosphination of vinyl glycine 131 [118], followed by the addition to an electro-deficient olefin 132 [119] and the methylation with trimethylsilyldiazomethane afforded phosphinate ester 133. 

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