Aminoethanol, methylation

Benzyl cyanide is first reacted with 2-butylbromide in the presence of sodium amide to give 2-phenyl-3-methylvaleronitrile which is hydrolyzed by sulfuric acid to give 3-methyl-2-phenyl-pentanoic acid. 24 g of 2-phenyl-3-methyl-pentanoic acid are heated for one hour at 175° to 185°C with 30 g of 2-diethylaminoethanol and 0.5 g of sodium methylate. The excess diethyl-aminoethanol is removed in vacuo, the residue is dissolved in 300 cc of 2 N-acetic acid, the acid solution is shaken with ether and made alkaline with concentrated potassium carbonate solution and ice. The ether solution Is washed with water, dried with sodium sulfate and evaporated. The residue is distilled under high vacuum, yielding 20 to 21 g of the basic ester (60% of the theoretical) is obtained, the ester boiling at 98° to 100°C at a pressure of 0.03 mm. The hydrochloride of the ester melts at 112° to 113°C and the methobromide at 100° to 101°C. 

N,N-Diethyl-2- [methyl(cyclohexyloxy)phosphoryl]sulfanyl -N-methylethanaminium Iodide N,N-Diethyl-2-aminoethanol N,N-Diethyl-2-hydroxyethylamine N,N-Diethylethanolamine N,N-Diethyl-N-(/3-hydroxyethyl)amine N,N-Diisopropyl-(jS)-aminoethanol N,N-Diisopropyl-2-aminoethanol /V,/V-I)i isopropylamine N,N-Diisopropylaminoethanol /V,/V,-l)iisopropylcarbodiimide N,N-Diisopropylethanolamine N,N-Dimethyl-2-chloroethylamine N/N -DimethyM -bipyridinium /V,/V,-I)imethylhydrazine N,N-Dimethyl-N-(2-chloroethyl)amine /V,/Vd)irnethyl-/i-chloroethylamine /V,/V,-Methanetetrayl Biscyclohexanamine /V./V -Thiod i-2,1 -ethanediyl Bis(N-isopropyl)-2-propanamine N,a-Dimethylphenethylam ine... 

Mesityl oxide Methanol Methylamine N- M et hy lformam i de Methyl isobutyl ketone 2-Aminoethanol, chlorosulfonic acid, nitric acid, ethylenediamine, sulfuric acid Beryllium dihydride, chloroform, oxidants, potassium fcrf-butoxidc Nitromethane Benzenesulfonyl chloride Potassium ferf-butoxide... 

First of all a 2-substituted oxazoline (1) is formed by cyclocondensation of a carboxylic acid ester with 2-aminoethanol and a small amount of (1) is converted with an alkylating agent (e.g., methyl tosylate) to the activated, ionic form (2). 

The synthesis of rosiglitazone is quite straightforward (Scheme 8.1). Reaction of 2-chloropyridine (11) with 2-(A-methylamino)ethanol (12) by heating at 150°C gave 2-[A-methyl-A-(2-pyridyl)]aminoethanol (13, 95% yield), which was then reacted with... 

Compound 98 was condensed with o-aminothiophenol, 2-aminoethanol, or cystamine in refluxing diphenyl ether through an intermolecular cyclization with the elimination of two molecules of water to give the polyfused derivatives 101-103, respectively. Also, the reactions of 98 with dimethylthiomethylenemalononitrile in boiling dimethylforma-mide (DMF) were studied. The dimethylthiomethylenemalononitrile was prepared via the reaction of malononitrile with CS2 with 2 equiv of methyl iodide in a one-pot reaction using liquid-liquid phase-transfer catalysis (PTC) technique (NaOH/dioxane/tetrabutylammonium bromide (TBAB)). The product of this reaction was identified as 8-cyano-9-imino-7-methylthio-6-oxo-3-phenyl-5,6,8,9-tetrahydro-77/-pyrano[3,2-/][l,2,4]-triazolo[3,4-A][l,3,4]thia-diazepine 104 (Scheme 10). 

For preparation of cyclopirox from l-hydroxy-4-methyl-6-cyclohexyl-2-pyridone was added 2-aminoethanol (1 1). 

Reaction of the l-aryl-2-phenacylcyclopropanes with chlorosulphonyl isocyanate and subsequent removal of the chlorosulphonyl group with benzenethiol in pyridine affords the 4,5-dihydro-1,3-oxazepines (91) <95SCI939> and in a reaction sequence in which an aziridine is the source of nitrogen, methyl l-benzyloxycarbonylaziridine-2-carboxylate reacts with 2-(N-benzyl-A -/t /7-butoxycarbonyl)aminoethanol to give the derivative (92) which, after removal of the Boc group, is subject to a reductive cyclisation to yield the hexahydro-l,4-oxazepine (93) <95CPBI 137>. 

In the seventh official proficiency test, one laboratory did not recover triethanolamine (CAS 102-71-6) or N,N -di isopropyl aminoethanol (CAS 96-80-0). The laboratory performed cation exchange on the water sample, evaporated it to dryness, and methylated it. Both chemicals may have been retained, at least partially, on the cation-exchange cartridge. 

Another way of obtaining similar compounds is by reaction of 4,5-dichloro-2-methyl-6-nitro-3(2//)-pyridazin-3-one (145) with aminoethanols <78JAP(K)53002499>. The 4-chloro substituent can be converted into pharmaceutically interesting groups. 

The catalysts usually encountered in this reaction are platinum oxide and Raney nickel. Cope and Hancock synthesized several alkyl-aminoethanols, using both catalysts (88). Although they prepared the compounds with Adams catalyst, they found Raney nickel to be also suitable at elevated temperatures and pressures. An 86% yield of 2-sec-butylaminoethanol was obtained from methyl ethyl ketone and... 

SYNS P-(METHYLAMINO)ETHANOL N-METHYL-AMINOETHANOL N-METHYXETHANOLAMINE METHYLETHYLOL.AMINE METHYL(P-HYDROXY-ETHYL)AMINE MONOMETHYL-AMINOAETHANOL (GERMAN) MONOMETHYLAMINOETHANOL N-MONOMETHYLAMINOETHANOL USAF DO-50... 

A suspension of 2-(benzylsulfanyl)-l-methyl-9-(triphcnylmethyl)-9A/-purin-6(lff)-one (4.5 g, 8.7 mmol) in 2-aminoethanol (25 mL, 41 mmol) was stirred for 30 min at 160 C. The reaction mixture was directly applied to DIAION HP-4 column chromatography. The product was isolated by eluting with 30% aq MeOH to give 0.42 g of 2-(2-hydroxyethylamino)-l-methyl-9-triphcnyl-9//-purin-6(l//)-one. SOCI, (8 mL) was immediately added to this compound and stirred at rt for 30 min. "fhe solvent (SOCI ) was evaporated under reduced pressure and EtOH was added to the residue. The resulting precipitate was collected by filtration and recrystallized (F.tOH/i-PrOH) yield 0.45 g (27%) white crystals mp 308-310 C. 

In addition 3-methylmorphol was condensed with /kdimethylamino-ethyl chloride to give 3-methyl-4-(/3-dimethylaminoethyl)-morphol [xxxvn], which was unaffected by sodium ethoxide at 150° C., but was degraded to 3-methyl-4-acetylmorphol [xxvn, R = Ac] and /S-dimethyl-aminoethanol on heating with acetic anhydride, and to morphol [xxi], /3-dimethylaminoethanol, and tetramethylethylenediamine on heating with hydrogen chloride [52],... 

Methoxy-4 8-diacetoxyphenanthrene [Lxxxm]. /3-Dimethyl-aminoethanol and [Lxxxm] are formed when i/r-codeinone [lxxxiv] is heated with acetic anhydride, but the main product of this reaction is triacetylthebenine [lxxxv, R = Ac] [89]. i/r-Codeinone methiodide and ethanol at 160° C. give 3-methoxy-4 8-dihydroxyphenanthrene [89-90], which on methylation affords 3 4 8-trimethoxyphenanthrene [90], identical with an authentic specimen prepared in the usual way from 2-nitroveratric aldehyde and 2-methoxyphenylacetic acid [67]. In this way the location of the hydroxyl group in i/r-codeine and allo- -codeine, at C-8, was proved. 

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