IV-Methylmorpholine

Scheme 5-5. Reagents and conditions a NaOCE Ph, THF/DMF 5 1, — 10°C to room temperature, b LiAlELt, Et20, reflux, c AC2O, Py. d (1) Cat. RuCh/NaKTt, CCI4/ MeCN/H20 1 1 1.5, room temperature. (2) LiOH, THF/H20 5 4, 0°C. (3) 2N HC1, Et20, 0°C to room temperature, e (1) IV-methylmorpholine, isobutylchloroformate, N-hydroxy-2-thiopyridone, THF, NEt3, TFIF, — 15°C, (2) t-butyl mercaptan, irradiation, THF, room temperature, f H2, 10% Pd/C, EtOFI. g Cat. ( -Pr)4NRu04, NMO, 4 A MS, CH2CI2, room temperature.

Sequential treatment of tertiary amines containing N-methyl or /V-benzyl groups with carbon disulphide and alkyl halides gives alkyl dithiocarbamates in good to excellent yields. Thus IV-methylmorpholine, carbon disulphide and methyl iodide in THF gave 91% of compound 306366. 

Chloro-4,6-dimethoxy-l,3,5-triazine (100) reacts with iV-methylmorpholine at 20 °C to yield an isolable quaternary triazinylammonium salt (101 R = Me, R, R = C4H8O). This salt can then be reacted with a carboxylic acid to yield a 2-acyloxy-4,6-dimethoxy-l,3,5-triazine (102), which, in turn, can be reacted with an amine to yield an amide (103). This sequence of reactions provides an explanation for the activation (formation of reactive ester) of the carboxylic acid function by 2-chloro-4,6-disubstituted-l,3,5-triazines (100) in the presence of hindered amines. Several other hindered amines may replace iV-methylmorpholine in the process, but unhindered amines such as triethylamine and tributylamine were inactive. ... 

Methyl isocyanoacetate, 1470 iV-Methylmorpholine oxide, 1997 Nickel, Hydrogen, Oxygen, 4820 Nitric acid, Sulfur dioxide, 4436... 

The synthetic strategy of preparing pyrazines by condensation of 2-keto aldoximes with a-amino nitriles is well represented by Taylor s pteridine synthesis, in which a variety of 2-amino-3-cyanopyrazine 1-oxides have been prepared by using aminomalononitrile <2002TL6747> as the amino nitriles. In the same fashion, some other a-amino nitriles, which are often the Strecker synthesis products, are converted into 2-aminopyrazine 1-oxides 160 (Scheme 44). The condensations are realized by treatment with iV-methylmorpholine <1993JOC7542>, and... 

The reactions of A -BOC-protected a-amino acids 424 and diazomethane in the presence of iV-methylmorpholine-polystyrene and isobutyl chloroformate resulted in formation of diazoketones 425, which, on treatment with indium(lll) triflate, were cyclized to 4-substituted-tetrahydro-l,3-oxazine-2,5-diones 426 in high overall yields (Scheme 82) <2006TL7969>. 

From the study of a microbially mediated oxidation of arteether 28b, sufficient quantities of 7a-hydroxy 180 and 15-hydroxy derivatives 182 were obtained to employ them as intermediates for the preparation of fluorinated compounds. The hydroxyl groups were oxidized to the corresponding aldehyde 187, or ketone 188, with catalytic quantities of tetra- -propylammonium perruthenate (TPAP) in the presence of excess iV-methylmorpholine A -oxide. On reaction with DAST, 187 and 188 were converted into the corresponding geminal difluoro derivatives, 189 (63%) and 190 (42%). In addition to 190, a monofluoro olefin 191 was obtained in 25% yield from 188 on reaction with DAST <1995JME4120>. 

BASF AG CRBPII dba DBN DBU DIBAL-H DMAP DMF DMF-DMA DMPU HMDS HMPA HMPT H-LR LDA LDE LRAT MCPBA MOM NMO NMP PCC PhH = Badische Anilin- Soda Fabrik AG = cellular retinol-binding protein type II r dibenzylideneacetone = 1,5-diazabicyclo[4.3.0]non-5-ene = l,8-diazabicyclo[5.4.0]undec-7-ene = diisobutylaluminium hydride = 4-dimethylaminopyridine = A V-dimethylformamide = A,V-dimethylformamide, dimethylacetal = 1,3 -dimethyl-3,4,5,6-tetrahydro-2( 1H)-pyrimidone = hexamethyldisilazane = hexamethylphosphoramide = hexamethylphosphorous triamide = Hoffmann-La Roche = lithium diisopropylamide = lithium diethylamide = lecithin retinol acyltransferase = m-chloroperbenzoic acid = methoxymethyl = iV-methylmorpholine oxide = l-methyl-2-pyrrolidinone = pyridinium chlorochromate = benzene... 

The use of triethylamine leads to a (1-elimination of MeOH from the product. This is avoided by employing the weaker base iV-methylmorpholine. 

Reaction of seven-membered anhydride with sodium sulfide in a 2 1 molar ratio afforded seven-membered thioanhydride and dicarboxylate in a 1 1 molar ratio (Equation 28) <1995JHC971>. The reaction of 199 gave 5,7-dihydrodibenzo[c/]thiepin-5,7-dione 200 in 77% yield. Seven-membered ring anhydrides synthesized in situ from the corresponding diacids 202 and 204 using iV-methylmorpholine and methyl chloroformate were treated with sodium sulfide in THF-HzO to form thioanhydrides 203 and 205 in 92-95% yield (Equations 29 and 30). 

Another approach for the synthesis of dioxazoline derivative 162 is achieved by Michael addition of benzohy-droxamic acid 161 to methyl propiolate, catalyzed by iV-methylmorpholine (Scheme 24) <2000TL7433>. 

Direct bridgehead alkynylation of 1-iodoadamantane has been achieved by treatment with a variety of silver acetylides at reflux in IV-methylmorpholine.114 The methodology has been extended to the direct bridgehead substitution of methyl-bicyclo[2.2.2]octane and a carborate anion (Scheme 1.50).115... 

Thiophene-2-carbaldehyde condenses easily with ethyl acetoacetate or ethyl nitroacetate in the presence of TiCl4 and a tertiary organic base (pyridine or iV-methylmorpholine) at 0-22 °C, giving (361) (72T663). Base-catalyzed condensation of thiophene-2-carbaldehyde with methyl (methylthio)methyl sulfoxide followed by treatment with HC1 in alcohols gives (2-thienyl)acetic esters (Scheme 114) (79BCJ2013). 

If no iV-methylmorpholine-iV-oxidc were added the ruthenium(V) acid would be converted into RuOz. In that case, Ru(VII) would be a three-electron oxidizing agent just like Cr(VI) (Figure 14.10). Such a conversion of Ru(V) into Ru(IV) could in principle occur, since Ru(V) also oxidizes alcohols. This oxidation presumably would proceed via an a-hydroxylated radical as discussed for the Cr(IV) oxidation of alcohols (Fig 14.10, center). Yet, there is no indication for such a radical pathway to occur when the reaction is carried out in the presence of A-methylmorpholine-A-oxide. Hence, it appears that A-methylmorpholine-A-oxide reoxidizes the ruthenium(V) acid to per-ruthenate faster than the ruthenium(V) acid could attack an alcohol molecule. 

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