Methyl iodide, esterification with

The original Garner preparation3 of 5 involves the conversion of serine into the protected methyl ester 3 and controlled reduction of the latter by DIBAL. The reaction sequence employed for the preparation of 3 involves the protection of the amino acid as N-Boc derivative using di-tert-butyl dicarbonate, esterification with methyl iodide or diazomethane, and acetonization with 2,2-dimethoxypropane under acid catalysis. The N-Boc methyl serinate and the ester 3 require purification by vacuum distillation or chromatography. In a modification to this procedure reported by McKillop,2 the esterification reaction of serine is carried out first by methanol/acetyl chloride. The resulting ester is then converted into the N-Boc derivative 2 with di-tert-butyl dicarbonate and the latter transformed into 3 by acetonization. This procedure avoids... 

Dielectric and electrophoretic measurements supported the hypothesis that zwitterions were formed. Electrophoretic mobility could be demonstrated for a polymer sample after its esterification with methyl iodide. 

Piperazine-2,5-dione treated with sodium hydride in A,A-dimethylacetamide and carbon disulfide followed by esterification with methyl iodide gave l-methylthio(thio-carbonyl)piperazine-2,5-dione (methyl 2,5-dioxopiperazine-l-dithiocarboxylate) and l,4-bis[methylthio(thiocarbonyl)]piperazine-2,5-dione (107), but when the reaction was carried out in dimethyl sulfoxide containing tetrahydrofuran it afforded (107) plus 3-[bis(methylthio)methylene]-l-methylthio(thiocarbonyl)piperazine-2,5-dione (108) (1630). 

We thank Dr. N. S. Chandrakumar of G. D. Searle and Company for alerting us to the fact that N-Boc-serine methyl ester could be prepared without significant racemization via esterification with methyl iodide, thereby avoiding the generation and use of diazomethane on a large scale. 

Although it is seldom used, esterification of pyrimidinecarboxylic acids proceeds normally. Conditions are illustrated by the conversion of pyrimidine-4-carboxylic acid (181 R = H) into its methyl ester (181 R = Me) by methanol/sulfuric acid (47%), methanol/hydrogen chloride (80%), or by diazomethane (ca. 100%) (60MI21300). The isomeric methyl pyrimidine-2-carboxylate is formed by treatment of the silver salt of the acid with methyl iodide. Higher esters, e.g. (182 R = Bu), are usually made by warming the acid (182 R = H) with the appropriate alcohol and sulfuric acid (60JOC1950). 

Ewins has synthesised both substances from m-methoxybenzoic acid, which on nitration gave 2-nitro-3-methoxybenzoic acid, and this, on reduction and treatment with methyl iodide, yielded damasceninic acid, which, by esterification with methyl alcohol, furnished damascenine. Kaufmann and Rothlen found that the additive product of 8-methoxy-quinoline and methyl sulphate, on oxidation with permanganate, yields formyldamasceninic acid, MeO. CgH3(NMe. CHO). COOH, which can be transformed into damasceninic acid by warming with dilute hydrochloric acid. ... 

Methylation of nicotine to the pyridinium iodide with methyl iodide, followed by its conversion to the hydroxide with silver oxide in water, oxidation with potassium permanganate to the A -methyl nicotinic acid hydroxide and subsequent deprotonation with silver oxide yielded Trigollenine as colorless needles (1897CB2117). In a later publication, the formation of nicotinic acid from nicotine was described. Esterification followed by aminolysis and methylation yielded the A -methylnicotinamide... 

The esterification of l-benzyM-(phenylamino) piperidine-4-carboxylic acid with ethanol and H2SO4 gives the corresponding ethyl ester, which is reduced with LiAIH2(0CH2CH20CH3)2 in benzene affording 1-benzyl-4-(phenylamino)piperidine-4-methanol. The methylation of this compound with methyl iodide and NaH in HMPA yields 1 -benzyl-4-methoxymethyl-4-(phenylamino)-... 

Sequential alkylation of the lithium enolate of 897 with methyl iodide and then allyl bromide furnishes dialkylated malate 938 with 96 4 diastereoselectivity. The hydroxyl group is removed via a xanthate ester to give 939, which is then alkylated with 4-bromo-l-butene to give 940 as the major isomer. The mixture is hydrolyzed with base and heated with urea to yield imides 941 and 942 in a 3 1 ratio. After isolation of pure 941 by crystallization, the remaining undesired diastereomer 942 is epimerized to 941 with potassium tert-hutoxide. Oxidation of 941 with ruthenium tetroxide-sodium periodate and esterification of the resulting acids furnishes imide 943. This sequence has produced more than 10 g of 943 in a single run. 

Alkylative esterification of carboxylic acids with alkyl halides are effected by action with TMG (1) [65]. An ester is given by the TMG (1) mediated reaction of y-hydroxy-a,p-unsaturated carboxylic acid with methyl iodide without lactone formation after isomerization [65a]. Barton s base effectively works in the alkylation of sterically hindered carboxylic acid [3]. Ethanolysis of the acetate of tertiary alcohol occurred easily in 86% yield in the presence of BTMG (2) [66] (Scheme 4.24). 

Note The value of this procedure lies mainly in the fact that when formaldehyde is used for the condensation N,N-dimethylamino adds can be conveniently prepared in this way [1311 whereas methylation of amino adds with methyl iodide in the presence of alkali leads to betaines, occasionally accompanied by monoalkylation. In the case of methylatioa commercial 40% formaldehyde in water serves as both the reagent and the solvent, and its amount should be at least twice the theoretical amount. Combined with suitable esterification [132, 133], volatile derivatives of many amino acids suitable for anlysis by GC are produced. 

The homogeneous reaction of tetrabutylammonium carboxylates (ion pair extraction) with methyl iodide in a two-phase system consisting of aqueous base and dichloromethane has also been reported. In most cases where the carboxylic acid was monobasic, excellent to quantitative yields of ester were observed. It was also noted that the esterification was insensitive to steric hindrance in the acid component under these conditions (see Eq. 6.4) [10]. 

Namely, the reaction of 2-thioxothiazolidin-4-one N-hexanoic acid (116) with 2,5-dimethyl-l-phenylpyrrol-3-carboxaldehyde (117) in methanol under the catalytic action of ethylenediamine diacetate (EDDA) yields 5-[(2,5-dimethyl-l-phenylpyrrol-3-yl)methylidene]-2-thioxothiazolidin-4-one N-hexanoic acid (118) in 79% yield. The hydroxamate derivative of 118 is prepared by reacting this compound with 0-(tetrahydro-2H-pyran-2-yl)hydroxylamine followed by treatment with p-toluenesulfonic acid in methanol to afford compound 121 in 60% yield. Esterification of compound 118 is carried out by using methyl iodide in acetonitrile in the presence of sodium carbonate to give compound 120. The 5-(cyclohexyl)methylidene analogue (119) is obtained in 42% yield by direct reaction of compound 116 with cyclohexanecar-boxaldehyde in methanol under the catalytic action of EDDA. 

In a working catalytic system, however, the principal solvent component is acetic acid, so esterification (Eq. 2) leads to substantial conversion of the substrate into methyl acetate. Methyl acetate is activated by reaction with the iodide co-catalyst (Eq. 3) ... 

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