Amino-alcohols ethers

The homolog of epinephrine in this series is a potent vasoconstrictor. Reaction of 3,4-dimethoxypropiophenone with butyl nitrite leads to nitrosation at the a position (36). Stepwise reduction of the nitrosoketone leads to the amino alcohol (37). Removal of the methyl ether affords racemic 38. Resolution of this last followed by separation of the (-) isomer gives levonor-defrine (38). ... 

Reaction of the glycol, 70, affords an oxazolidinone rather than the expected carbamate (71) on fusion with urea. It has been postulated that the urea is in fact the first product formed. This compound then undergoes 0 to N migration with loss of carbon dioxide reaction of the amino alcohol with the isocyanic acid known to result from thermal decomposition of urea affords the observed product, mephenoxolone (74) this compound shows activity quite similar to that of the carbamate. An analogous reaction on the glyceryl ether, 75, affords metaxa-lone (76). 

Step 4 A solution of 20 grams of the above amino alcohol is dissolved in 50 ml of dry chloroform and treated with dry hydrogen chloride until acid. Then a solution of 9 grams of thionyi chloride in 50 ml of dry chloroform is added and the reaction mixture is heated on a water bath at 50°-60°C for 2 hours. Most of the chloroform is removed by distillation under reduced pressure. Addition of ether to the residue causes the product to crystallize. After recrystallization from a mixture of alcohol and ether, the N-(phenoxyisopropyl)-N-benzyl-0-chloroethylamine hydrochloride melts at 137.5°-140°C. 

The resulting product was dissolved in water, made alkaline with dilute NH4OH and was extracted with ether. After evaporation of the ether, the amino-alcohol was obtained as a base. 

A solution of 3.7 g (12 mmol) of the pure (l R)-diastereomer 6 is stirred under nitrogen in 15 mL of iodomethane and 5 mL of dry DMSO for 36 h. The excess iodomethanc is evaporated leaving a viscous red oil which is heated under reflux in 25 mL of 2N KOI for 5 h. After cooling, the amino alcohol is removed from the aqueous phase by extraction with Et20. The alkaline aqueous layer is acidified with 12 N HC1 and extracted with Ei,0. The crude product is recrystallized from benzene/petroleum ether to give enantiomer-ically pure (R)-2-hydroxy-2-phenylpropanoic acid [(-)-(R)-atrolaclic acid] (7) yield 1.4 g (71%) mp U5-116X [x]25 - 38.4 (< = 2.5, EtOH). 

Amino alcohols and ethers (C6H14NO) iV-TFA, /7-butyl glutamic acid... 

Asymmetric addition to ketimine in a reagent controlled manner has seldom been reported, even by 2008. When we investigated the potential for tbis asymmetric addition around 1992, there were no known examples. In 1990, Tomioka et al., reported the first asymmetric addition of alkyl lithium to N-p-methoxyphenyl aldo-imines in the presence ofa chiral (3-amino ether with 40-64% ee [8] (Scheme 1.11). In 1992, Katritzky reported the asymmetric addition of Et2Zn to in situ prepared N-acyl imine in the presence of a chiral (3-amino alcohol with 21-70% ee [15] (Scheme 1.12). In the same year, Soai et al., reported the asymmetric addition of dialkylzinc to diphenylphosphinoyl imines in the presence of chiral (3-amino alcohols with 85-87% ee [16] (Scheme 1.13). These three reports were, to the best of... 

The variety and extent of research devoted to ligands carrying both O- and N-donors is simply immense. The type of cobalt(III) systems extant include amino acids, amino alcohols, amino ethers, amino phosphates, amino phenolates, as well as amide and imine analogs of these. These are met as simple chelates or more elaborate polydentates. Here, we highlight a strictly limited selection of examples to illustrate the type of systems reported no attempt at exhaustive review has been made. 

They react with a wide range of aliphatic and aromatic aldehydes in the presence of catalytic amounts of tetrabutylammonium fluoride (TBAF) to give the trialkylsilyl ethers of P-nitro alcohols with high anti-selectivity (98%). The diastereoselective Henry reaction is summarized in Table 3.2. The products are reduced to P-amino alcohols using Raney Ni-H2 with retention of the configuration of P-nitro alcohols (Scheme 3.12). 

Ono and Kamimura have found a very simple method for the stereo-control of the Michael addition of thiols, selenols, or alcohols. The Michael addition of thiolate anions to nitroalkenes followed by protonation at -78 °C gives anti-(J-nitro sulfides (Eq. 4.8).11 This procedure can be extended to the preparation of a/jti-(3-nitro selenides (Eq. 4.9)12 and a/jti-(3-nitro ethers (Eq. 4.10).13 The addition products of benzyl alcohol are converted into P-amino alcohols with the retention of the configuration, which is a useful method for anri-P-amino alcohols. This is an alternative method of stereoselective nitro-aldol reactions (Section 3.3). The anti selectivity of these reactions is explained on the basis of stereoselective protonation to nitronate anion intermediates. The high stereoselectivity requires heteroatom substituents on the P-position of the nitro group. The computational calculation exhibits that the heteroatom covers one site of the plane of the nitronate anion.14... 

Phospholipids are also found which have similar structures (Table 12.6). These include lysophospholipids, which have only one of the two possible positions of glycerol esterified, almost invariably at carbon 1, and the plas-malogens, in which there is a long chain vinyl ether at carbon 1 instead of a fatty acid ester. These compounds also contain an amino alcohol, which may be either serine, ethanolamine or choline. Other rarer phospholipids are the monoacyl monoether, the diether and the phosphono forms. 

The reduction of phenyl mesityl ketone was studied with LAH modified with amino alcohols 65 to 72 in ether (the ratio LAH alcohol ketone = 1.1 1.1 1) (83). Optical yields were modest, with the highest 39%, obtained with 65 as the chiral auxiliary reagent. It was observed that there is a relationship between the preferred enantiomeric product and the structure and absolute configuration of the carbons carrying the hydroxy and amino groups. Thus the threo... 

In ether solvent ratio LAH amino alcohol ketone = 1.1 1.1 1. 

Mole ratio amino alcohol LAH = 4.1 1.8. Reaction carried out at - 70°C with insoluble, freshly prepared complexes in ether. Analysis by GC of MTPA ester derivatives. 

In a soluble polymer strategy comparable to resin-capture [145], Janda reported a MeO-PEGsooo-supported dialkyl borane reagent (31) that was used in the purification of a solution-phase library of y9-amino alcohols [146]. Purification was achieved by simply adding (31) to the crude reaction mixture followed by subsequent precipitation of the polymer with diethyl ether to give polymer-supported 1,3,2-oxazaboroU-dine (32) (Scheme 5.2). The /9-amino alcohol product could then be released from the soluble support by treatment with acid. In a two-step synthetic strategy that is readily amendable to automation, the isolation of a small library of /9-amino alcohols was accomplished with all compounds obtained in >80% purity. 

Alkylaminotetrahydropyrans may be considered derivatives of aldehydes. They are reductively cleaved by lithium aluminum hydride to amino alcohols. Thus 2-(iV-piperidyl)tetrahydropyran afforded, after refluxing for 2 hours with 2 mol of lithium aluminum hydride in ether, 5-piperidino-l-pentanol in 82% yield [507]. 

Cdrdova has shown that using unprotected iV-hydroxycarbamates 71 as the nucleophile with diarylprohnol ether 30 as catalyst gave direct access to 5-hydrox-yisoxazolidines 72 (91-99% ee) which are convenient precursors to p-amino alcohols and p-amino acids (Scheme 31) [110], Interestingly, these reactions proceed efficiently (3-16 h) without the need for an additional co-acid unlike the majority of other iminium ion catalysed transformations, an unexpected result which highlights the need for further mechanistic understanding. 

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