Ephedrine yields

Reductive czonolysis of 15-acetoxy-prostanoids followed by reaction cf the resulting 2-acetoxy-heptanal with i-ephedrine yielded oxazolines whose values on t.l.c. are characteristic of... 

Efdiedrine, CnHjsON, crystallises from ether in rhombs, m.p. 118-9 , Md + 51 2 (EtOH), and, unlike ephedrine, is sparingly soluble in water. The hydrochloride, B. HCl, crystallises in colourless, slender needles, m.p. 181-2 , [a] -f- 62-05 (HjO), and, unlike the ephesulphate forms prisms, [a]i> + 52-5 the oxalate, m.p. 218 (dee.), unlike that of ephedrine, is readily soluble in water the aurichloride has m.p. 126-5-127-5 . Nitroso-0-ephedrine has m.p. 86 , and dibenzoyl- -ephedrine melts at 119-120 . By Mitchell s process d- -ephedrine yields an acetyl derivative, m.p. 103-5-104 ,... 

In this thiamine pyrophosphate-mediated process, ben2aldehyde (29), added to fermenting yeast, reacts with acetaldehyde (qv) (30), generated from glucose by the biocatalyst, to yield (R)-l-phen5l-l-hydroxy-2-propanone (31). The en2ymatically induced chiral center of (31) helps in the asymmetric reductive (chemical) condensation with methylamine to yield (lR,23)-ephedrine [299-42-3] (32). Substituted ben2aldehyde derivatives react in the same manner (80). 

The world war made all these sources of supply difficult of access and stimulated interest in the possibilities of local production. Examination of a number of American species of ephedra had already shown them to be devoid of alkaloids, except for the S. American species E. andina, in which Chavezt found ephedrine, and in the United States attention has been given to the experimental cultivation of imported species, notably E. sinica and E. gerardiana a Moroccan type, E. alenda, was found to contain only ). In Australia experimental cultivation of the Indian species E. gerardiana, E. intermedia and E. nebrodensis has been tried and preliminary yields of 1-35, 1-OS and 0-98 per cent, of total alkaloids respectively have been recorded. In Russia, E. equisetina and E. intermedia are available and are considered to be worth exploitation. In Italy various local species have been found to contain mainly i -ephedrine and that in small amount, but better results are recorded for two species already referred to and which are available in Sardinia, viz. E. vulgaris Rich and E. nebrodensis. ... 

The total alkaloidal eontent of Ephedra varies widely, being influeneed by the speeies eolleeted and the seasonal and environmental eonditions, as has been shown by Read and by Chopra and their eolleagues. For speeially eolleeted material yields as high as 2- 56 per cent., of which 1- 8 per cent, is ephedrine, have been recorded, but about 1 per cent, of total alkaloids is not usually exceeded in the commercial product. 

Mannich condensation of the primary amine corresponding to ephedrine (32) with formaldehyde and m-methoxyacetophenone yields oxyfedrine (33), this agent retains the vasodilating activity of ephedrine and is in fact denoted a coronary vasodilating agent. 

Addition of a hydroxyl group to the aromatic ring of ephedrine as well as changing the substitution on nitrogen leads to a compound whose main activity is to raise blood pressure. Thus, lormation of the Shiff base of the m-hydroxy analog of 30 with bcnzylamine (34), followed by catalytic reduction, yields metar- uiiinol (35). When optically active hydroxyketone is employed in... 

Conjugate addition of chiral amines to allenic and acetylenic sulfones has been reported73. The reaction 112 with (—)-ephedrine gives only one of the two possible diastereomeric oxazolines in high yield (equation 89). 

Aromatic ethanolamine derivatives, e.g. ephedrine, also yield blue-colored chelates with Cu + ions (Chen-Kao reaction [4, 27]). 

A Cp2ZrCl2-catalyzed addition of Bu2AlH to terminal alkynes has been applied in the synthesis of (E)-vinyl phosphonates [84]. 1-Hexyne and 1-octyne were hydroalu-minated at 0°C and the resulting vinylalanes transformed into the respective alumi-nate complexes by treatment with methyllithium. Subsequent addition of oxaza-phospholidinone 79, derived from (-)-ephedrine, lead to the homochiral vinyl phosphonates in yields of ca. 75% (Scheme 2-23). 

In the same study, these authors have prepared another series of amino-sulf(ox)ide ligands based on the (Nor)ephedrine and 2-aminodiphenylethanol skeletons, bearing two chiral centres in the carbon backbone.Their application to the iridium-catalysed hydrogen-transfer reduction of acetophenone generally gave better yields, but the enantioselectivity never exceeded 65% ee (Scheme 9.4). 

Introduction Since we had already developed the novel asymmetric addition of lithium acetylide to ketimine 5, we did not spend any time on investigating any chiral resolution methods for Efavirenz . Our previous method was applied to 41. In the presence of the lithium alkoxide of cinchona alkaloids, the reaction proceeded to afford the desired alcohol 45, as expected, but the enantiomeric excess of 45 was only in the range 50-60%. After screening various readily accessible chiral amino alcohols, it was found that a derivative of ephedrine, (1J ,2S) l-phenyl-2-(l-pyrrolidinyl)propan-l-ol (46), provided the best enantiomeric excess of 45 (as high as 98%) with an excellent yield (vide infra). Prior to the development of asymmetric addition in detail, we had to prepare two additional reagents, the chiral modifier 46 and cyclopropylacetylene (37). 

The condensation of enantiomerically pure amino alcohols (derived from amino acids) with aldehydes to furnish 1,3-oxazolidines was studied by Kuhnert and Danks in 2001 (Scheme 6.212) [382], Under solvent-free conditions, microwave irradiation of equimolar mixtures of the amino alcohol and the aldehyde for less than 3 min provided high isolated yields of 1,3-oxazolidines with excellent diastereoselectivity. In the case of (-)-ephedrine, prolonged microwave irradiation (3 min) produced quantitative conversions and high diastereoselectivities. For shorter irradiation times (80 s) mixtures of the two diastereomers were obtained with moderate conversions. 

C. (+)- and (-)-a-(Isopropylideneaminooxy) propionic acid-(-)-ephedrine salts. A solution of 36.6 g. (0.200 mole) of (— )-ephedrine monohydrate (Note 7) in 800 ml. of ethyl acetate containing 6% of ethanol (Note 8) is placed in a 2-1. beaker, d,l-a-(Isopropylideneaminooxy)propionic acid (29.0 g., 0.200 mole) is dissolved in this solution by stirring (Note 9). The beaker is covered securely with a rubber dam, cooled for a short period in an ice bath, placed in a refrigerator at 0-5°, and allowed to remain undisturbed for 8-16 hours after crystallization has begun (Note 10). The solid mass of crystals is filtered by suction, and the funnel is covered with a rubber dam to remove most of the solvent. The solid product is placed in a 500-ml. beaker, 250 ml. of ethyl acetate is added (Note 11), and the mixture is heated until all the solid has dissolved. The solution is cooled, placed in a refrigerator for several hours, and filtered the crystalline precipitate is dried in air. The yield of the (—)-ephedrine-(+)-a-(isopropylideneaminooxy)propionic acid salt is 22-25 g. (71-81%) m.p. 115-119° (Notes 12 and 13) [ ]2°d -4.2° (c 1.5, chloroform). 

The combined filtrates are diluted with an equal volume of petroleum ether (b.p. 30-60°), placed in a refrigerator for 8-16 hours, and filtered. The solid product is recrystallized from ethyl acetate (10 ml. per gram of the salt). The yield of the monohydrate of the (—)-ephedrine-(—)-a-(isopropylideneami-nooxy)propionic acid salt is 19-26 g. (58-79%) m.p. 88-90° [a]20D —57° (c 1.5, chloroform) (Notes 13 and 14). 

Despite the high sensitivity of the methods for chiral resolution described in Section IV.D.4, more direct methods are afforded by NMR spectroscopy, especially for the products of synthesis. Ephedrine (179), pseudoephedrine (180a) and its Me ether (180b) yield stable epimeric N — BH3 adducts on treatment with borane. The configuration of the nitrogen moiety was established by NMR, taking into account the conformational analysis of the molecule392. 

Stereoselective reduction of a,(i-unsaturated ketones using lithium aluminium hydride has only been reported in conjunction with the ephedrine bases either in a two-phase system (80-90% yield, ee >70%) or immobilized on a polymer [18, 19]. 

---