Pseudoephedrine additions

SYMPATHOMIMETICS OXYTOCICS Risk of t BP when oxytocin co-administered with ephedrine, metaraminol, norepinephrine or pseudoephedrine Additive vasoconstriction Monitor PR, BP and ECG closely start inotropes at a lower dose... 

The oxazasilolidine derived from pseudoephedrine incorporates chirality around the silicon and leads to enantioselective addition. 

Decongestants such as OTC pseudoephedrine are sympathomimetic agents that constrict capacitance vessels in the nasal turbinates.17 Decongestants effectively reduce nasal congestion and to some extent rhinorrhea associated with AR.8,12 The recommended dose of pseudoephedrine is 30 to 60 mg every 4 to 6 hours for a maximum daily dose of 240 mg.15 Systemic adverse effects such as irritability, dizziness, headache, tremor, tachycardia, and insomnia can occur. Additionally, use is associated with increased blood pressure and intraocular pressure and urinary obstruction.8,12... 

The same laboratory has prepared three tridentate zinc chelates from chiral tertiary amino phenolic alcohols and used them for enantioselective addition of diethylzinc to aryl aldehydes in 70-87% ee. Results with the ligand 4 [from (1S,2S)-(+ )-pseudoephedrine] are typical. 

As would be expected, the first order spectrum of pseudoephedrine, shown in Figure 4.16, gives maxima at the points where the slope is at a maximum in the zero order spectrum. In addition, the second order spectrum gives minima corresponding to the maxima in the zero order spectrum, i.e. where the negative curvature of the spectrum is at its maximum. 

Clemastine, 1.34 mg every 12 hours Tavist Allergy have minimal anticholinergic effects and are therefore associated with a lower incidence of sedation. Occasionally, symptoms unrelieved by the antihistamine respond to the addition of a sympathomimetic decongestant. OTC sale of products containing pseudoephedrine is restricted (see comments under Decongestants, systemic). 

A. (1 S,2S)-N-(2-Hydroxy-1 -methyl-2-phenylethyl)-N-methylpropionamide, ((1S,2S)-pseudoephedrinepropionamide). A flame-dried, 1-L, round-bottomed flask equipped with a Teflon-coated magnetic stirring bar is charged with 21.3 g (129 mmol) of (1S,2S)-(+)-pseudoephedrine (Note 1) and 250 mL of tetrahydrofuran (Note 2). The flask is placed in a water bath at 23°C, and to the well-stirred solution, 18.0 g (138 mmol) of propionic anhydride (Note 3) is added by a Pasteur pipette in 1-mL portions over approximately 5 min. The flask is sealed with a rubber septum containing a needle adapter to an argon-filled balloon, and the clear, colorless solution is allowed to stir at 23°C for an additional 10 min. The rubber septum is removed, and the reaction solution is neutralized by the addition of 400 mL of saturated aqueous sodium bicarbonate solution. After thorough mixing (Note 4), the biphasic mixture is poured... 

This procedure describes the use of pseudoephedrine as a chiral auxiliary for the asymmetric alkylation of carboxylic acid amides. In addition to the low cost and availability in bulk of both enantiomeric forms of the chiral auxiliary, pseudoephedrine, a particular advantage of the method is the facility with which the pseudoephedrine amides are formed. In the case of carboxylic acid anhydrides, the acylation reaction occurs rapidly upon mixing with pseudoephedrine. Because pseudoephedrine amides are frequently crystalline materials, the acylation products are often isolated directly by crystallization, as illustrated in the procedure above. 

This operation is necessary to hydrolyze the pseudoephedrine aminal which forms as a direct product of the reduction, in addition to the desired aldehyde. The use of the additional 700 mL of 1 N aqueous hydrochloric acid solution was found to be crucial for this hydrolysis reaction. 

The pH of the aqueous phase following the addition of sodium bicarbonate is approximately 4. If the pH is less than 4, additional sodium bicarbonate should be added until the pH is 4 or slightly above. Small amounts of the pseudoephedrine aminal remain at this point, but are hydrolyzed during the rotary evaporation step. 

In addition to quenching excess hydride, the acidification and subsequent extraction steps remove pseudoephedrine and any tertiary amine reaction by-product the latter is otherwise difficult to remove by column chromatography. 

In a separate step of the process, either (IS, 2S)-(+)-pseudoephedrine (37) or /V-methyl-( IS, 2K)-cisA -amino-2-indanol (38) was successfully used as auxiliaries for the chiral Michael addition of an aryllithium to give compound 39 (Scheme 23.11).57... 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

In this context, it has been observed that dilithio derivative 333 cyclizes in the presence of TMEDA to give a dilithiated indoline that may be differentially functionalized by sequential addition of electrophiles, affording 1,3-disubstituted indolines 334 (Scheme 86)147. This cyclization reaction also proceeds in an enantioselective way when it is carried out in the presence of the pseudoephedrine ligand 332a. However, (—)-sparteine is in this case not able to promote the carbolithiation step, showing that the substrate structure may have a pronounced effect on the ability of a given ligand to facilitate the cyclization reaction. 

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