N- Methylmorpholine

LEY - GRIFFITH Oxidation reagent Oxidation ol alcotwls to caitxnyl compounds with a pemjthenate catalyst and N-methylmorpholine - N-oxIde (NMO), In the presence of other functional gmups... 

N-Methylmorpholine Oxide-Hydrogen Peroxide Oxidation. The preparation of A-methylmorpholine oxide-hydrogen peroxide is described in Reagents for Organic Synthesis by L. Fieser and M. Fieser. 

Pivorarenko and Khilya investigated a series of organic bases including tribenzyl amine, sodium methylate, sodium terf-butylate, n-methylmorpholine,... 

In 400 ml of dimethylformamide was dissolved 15.0 g of bleomycinic acid (copper-containing form). To the solution kept at 0°C by cooling were added 1.1 ml of N-methylmorpholine and 10.3 g of 6-chloro-1 -p-chlorobenzenesulfonyloxybenzotriazole (CCBT) as an activating compound. The mixture was stirred for 5 minutes at 0°C, then admixed with 5.3 g of N-[(S)-1 -phenylethyl] -1 3-diaminopropane and further stirred for 1 hour. 

Ley et al. reported oxidation of alcohols catalyzed by an ammonium perruthenate catalyst dissolved in [NEtJBr and [EMIM][PFg] [60]. Oxygen or N-methylmorpholine N-oxide is used as the oxidant and the authors describe easy product recovery by solvent extraction and mention the possibility of reusing the ionic catalyst solution. 

Initiation Mechanism of Persulfate-Amine N-methylmorpholine [46], which involves the formation ... 

TMSOTf 20 (0.056 mL, 0.29 mmol) is added to 1466 (0.50 g, 0.14 mmol) and N-methylmorpholine (0.03 mL, 0.28 mmol) in 8 mL abs. 1,2-dichloroethane and the mixture is stirred for 2 h at room temperature then heated under reflux for 8 h while removing most of the 1,2-dichloroethane by distillation. The residue is dissolved in toluene, further amounts of N-methylmorpholine (0.03 mL) and TMSOTf 20 (0.056 mL) are added, and the mixture is heated under reflux for 1 h, with exclusion of humidity, while removing the toluene by distillation. The residue is taken up in CH2CI2, washed with sat. NaHCOs solution, dried, and evaporated to give 0.47 g crude product, which is chromatographed in toluene on 5 g silica gel. After a pre-run of 175 mL toluene, the next 250 mL toluene elute 21 mg (45.7%) pure 1467, identified by MS (m/e=421) and NMR [30] (Scheme 9.51). 

As demonstrated by Hoffmann and coworkers, hydroformylation can also be combined with an allylboration and a second hydroformylation, which allows the formation of carbocycles and also heterocycles [213]. A good regioselectivity in favor of the linear aldehyde was obtained by use of the biphephos ligand [214]. Reaction of the allylboronate 6/2-76 having an B-configuration with CO/H2 in the presence of catalytic amounts of Rh(CO)2(acac) and biphephos led to the lactol 6/2-80 via 6/2-77-79 (Scheme 6/2.17). In a separate operation, 6/2-80 was oxidized to give the lactone 6/2-81 using tetrabutyl ammonium perruthenate/N-methylmorpholine N-oxide. 

A recent study concerned the microwave-assisted parallel synthesis of di- and tri-substituted ureas utilizing dedicated 96-well plates in the CombiCHEM system [60], In a typical procedure, modification of the Marshall resin utilized was achieved by treatment with p-nitrophenyl chloroformate and N-methylmorpholine (NMM) in dichloromethane at low temperatures. The resulting resin was further modified by attaching various amines to obtain a set of polymer-bound carbamates (Scheme 7.48). 

Nitrile oxides are oxidized by tertiary amine N-oxides, for example, N-methylmorpholine N-oxide, in various solvents at room temperature to unstable nitrosocarbonyl compounds. In the presence of dienes, such as 1,3-cyclo-hexadiene, they afford Diels-Alder adducts, e.g., 372 fromPhCNO, in fair yields. The mild conditions used in oxidizing a variety of nitrile oxides promise a wide application of this method in synthetic processes (420). 

With these solid supports in hand, we turned our attention to a new route to the synthesis of our target molecule 23 (Scheme 8). The tricky reductive amination should be replaced by an N-alkylation. To that end, bromoacetic acid is attached to 24c using DIC and Hiinig s base followed by the nucleophilic substitution with the corresponding benzy-lamine in DMSO/toluene (1 1), which can be easily monitored by the Beilstein test, followed by sulfonamide formation in DCM using N-methylmorpholine as base. For the final cleavage, 2% TFA in DCM is used and the resulting solution is filtered in a saturated NaHCC>3 solution to neutralise the acid before evaporation of the solvent. The crude product was then crystallised from ethyl acetate/heptane to yield the desired product in 27% yield overall and 99A% HPLC purity (see Table 4). 

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