Amino alcohols hydrochlorides

A suspension of the (i-amino alcohol hydrochloride 26 (0.4 g, 1.57 mmol), Ac-Leu-OH (0.27 g, 1.57 mmol) and NMM (0.17 tL, 1.57 mmol) in anhyd THF (10 mL) was stirred at 0°C for 3 min. 2M DCC in THF (0.75 pL) was added dropwise with stirring, the mixture was gradually warmed to rt while stirring for a total of 4 h, after which it was chilled, filtered, and concentrated. The concentrate was redissolved in EtOAc, washed with 0.3 M HC1,5% NaHC03, and sat. brine, then concentrated and flash chromatographed (CHCI / MeOH 15 1) to give the coupled product as an amorphous white solid yield 380mg (65%). 

Imino-l,3-selenazolidines have been prepared using potassium selenocyanate thus, 2-imino-l,3-selenazolidines 86, 87 resulted from reactions of 0-methanesulfonyl /3-amino alcohol hydrochlorides. The products retained the chirality introduced by the amino alcohol fragment (Equations 25 and 26) <2005BML1361, 2005TL233, 1997TA3903>. 

Imino-thiazolidine 93 is prepared directly from the corresponding (9-methanesulfonyl (3-amino alcohol hydrochloride 89 using potassium thiocyanate via aziridine intermediate 90 <05TL233>. Ring opening of 90 with potassium thiocyanate gives amines 91 and 92, which recyclizes to furnish the same cis itnine 93. 

Several 2-imino-l,3-selenazolidine derivatives 295 and 297 are prepared in the same fashion as their 1,3-thiazolidine counterparts as described in section 5.5.2.3 from the corresponding (9-methanesulfonyl P-amino alcohol hydrochlorides 294 and 296, respectively, using potassium selenocyanate <05TL233>. 

X- = AcO- Amberlyst A-26 Acetates from prim, iodides acetamido diols from iodo amino alcohol hydrochlorides (via aziridines). 95 NHs Cr NHAc OH HO ,A. R 1 OH NHAc... 

The major cycloadduct 29 readily separable from 30 by recrystallization, underwent catalytic hydrogenation to give the amino alcohol hydrochloride 31 which was in turn selectively N-acylated with ethyl chloroformate affording the carbamate 32 in 84% overall yield. Chlorination of 32 with thionyl chloride and excess of pyridine in chloroform at reflux yielded the chloride 33 (55%) along with a byproduct assigned the dicycloheptyl sulfite 34 (28%). Similarly, treatment of 35, prepared from 31, with thionyl chloride and pyridine gave 36 (36%) and 37 (38%). 

Scheme 2.70 Ni-catalysed synthesis of anti /i-amino alcohol hydrochlorides.

Mao, J., Wan, B., Wu, F. and Lu, S., First example of asymmetric transfer hydrogenation in water induced by chiral amino alcohol hydrochloride. Tetrahedron Lett., 2005, 46, 7341. 

To prepare the hydrochloride, dissolve about 1 g. of the compound (which need not be perfectly dry) in about 8 ml. of alcohol. Add this solution to boiling dilute hydrochloric acid (10 ml. of the concentrated acid and 80 ml. of water). Boil for 5 minutes, filter the hot solution if necessary, and allow to cool. p-Amino-azobenzene hydrochloride separates in steel-blue crystals. Filter, wash with a little dilute hydrochloric acid, and dry. 

Phenylpropanolamine. - With catalyst prepared as previously described from 0.5g of palladium chloride and 3g of charcoal, it was possible to reduce two portions of 9.8g of isonitrosopropio-phenone (0.06 mol), dissolved in 150 cc. of absolute alcohol containing 7. Og of hydrogen chloride, to phenylpropanolamine in from 145 - 190 minutes with yields of the isolated chloride from 9.4g to 11. Og, or 84 to 98% of the theoretical. After recrystallization from absolute alcohol the salt melted at 191°. The free base was obtained by treating an aqueous solution of the hydrochloride with alkali on cooling, the liberated amino alcohol solidified and after recrystallization from water melted at 103°."... 

An unusual by-product was obtained in small yield in palladium-catalyzed reduction of 2-amino-4,5-dimethoxyindanone hydrochloride, The reduction was done in two stages first, a rapid absorption of 1 mol of hydrogen at 38 C to give the amino alcohol, and then a much slower reduction in the presence of HCIO4 at 70 "C. The rearranged by-product was shown to arise from attack of acid on the amino alcohol (50), Resistance to hydrogenolysis is characteristic of / -amino aromatic alcohols (56), a fact that makes reduction of aromatic oximino ketones to amino benzyl alcohols a useful synthetic reaction. 

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. 

Reaction of (S)-(+)-2-aminobutyrate hydrochloride with ethyl oxalyl chloride followed by replacing of the ethyl ester with amino alcohol, oxidation with Dess-Martin periodinate and cyclization using TFA/TFAA in acetic acid gave the cyclic product, which was further converted to the bromide. Sub-... 

Aliphatic and aromatic nitriles are often converted to the corresponding imidates that then react with amino alcohols to provide oxazolines. This two-step process offers milder conditions. Generally, a mixture of the imidate (free base or hydrochloride) is allowed to react with the amino alcohol in a solvent (alcohols, CH2CI2, CHCI3) with or without a tertiary base. As expected, the cylization proceeds with retention of stereochemistry when chiral amino alcohols are used. Representative examples are shown in Table g 17 33,62,63,139,216-225 ready availability of benzimidates and trimethyl orthobenzoates make them ideal surrogates for benzonitrile. ... 

The 1,3-proton shift reaction has also been applied to the synthesis of a-(perfluoroalkyl)-a-amino acids, specifically 3.3,3-trifluoroalanine.2 -26 Attempts to prepare the A-benzylimine of ethyl 3,3.3-trifluoro-2-oxopropanoate by direct condensation with benzylamine were very difficult due to the exceptionally high stability of the intermediate a-amino alcohol, which fails to dehydrate. By contrast, 1-phenylethanamine reacted with ethyl 3,3,3-trifluoro-2-oxo-propanoate to form ketimine 33 in 83 % yield.26 The 1,3-proton shift reaction of 33 is much faster than those of ketimines derived from perfluoroalkyl ketones or perfluoroaldehydes (see Table 5). Complete conversion in triethylamine required 6 hours at room temperature and afforded the isomeric Shiff base 34 in 92 % yield. Mild hydrolysis of Shifif base 34 gives a-amino ester 35, which in turn hydrolyzes to 3,3,3-trjfluoroalanine hydrochloride (36). 

Pioneering studies on the asymmetric hydrogenation of a-amino ketones have been done by Kumada and Achiwa [3, 4]. Achiwa s MCCPM/Rh complex catalyzed the reaction of 2-(dimethylamino)acetophenone hydrochloride with an Si C of 100,000 under 20 atm of H2 to give the corresponding chiral amino alcohol in 96% ee [32], although the reactions of other amino ketones showed less satisfactory rates and enantioselectivity. 

The use of a cationic aza-Cope rearrangement in concert with a Mannich cyclization has also been applied to the total synthesis of enantiomerically pure (—)-crinine (359) (205). In the event, nucleophilic opening of cyclopentenoxide with the aluminum amide that was formed on reaction of (/ )-a-methylbenzyl-amine and trimethylaluminum gave the amino alcohol 485 together with its (15,25) diastereomer. Although there was essentially no asymmetric induction in this process, the diastereomeric amino alcohols were readily separated by chromatography, and the overall procedure therefore constitutes an efficient means for the preparation of enantiomerically pure 2-amino alcohols from epoxides. When the hydrochloride salt derived from 485 was treated with paraformaldehyde and potassium cyanide, the amino nitrile 486 was formed. Subsequent Swem oxida-... 

The synthesis of 3-alkyl-substituted 1,2-thiazetidine 1,1-dioxides starts by transformation of the amino acids L-Val, L-Leu, L-Ile, and L-Phe into amino alcohols. These ate converted via the bromides to the corresponding thiols 161. Immediate oxidative chlorination affords either sulfonyl chloride hydrochlorides or sulfonic acids 162 which are transformed into the parent /3-sultams 163 <2004HCA90>. Similarly, L-cystine derivatives 164 have also been transformed into the parent /3-sultams 165 by oxidative chlorination followed by cyclization (Scheme 50) C1997LA1261, 2004HCA90>. 

Application of the Mettler RC1 Reaction Calorimeter in Optimizing a Process for the Reduction of Methyl (S)-Phenylglycinate. The sodium borohydride reduction of methyl (S )-phenylglydnate (hydrochloride salt) to the corresponding primary amino alcohol (Scheme 4) had been worked out in the laboratory and taken to a pilot plant scale where an unexpected exotherm was observed. 

The solution is evaporated to dryness under reduced pressure on a water bath. In order to remove as much hydrochloric acid as possible, the temperature of the bath is raised to 100° toward the end of the distillation. The residue of amino acid hydrochloride and inorganic salts is suspended in 500 cc. of absolute ethyl alcohol. The suspension is boiled on a steam bath for a short time, then cooled to room temperature and filtered on a Buchner funnel. The residue of inorganic salts is washed with 500 cc. of absolute ethyl alcohol. To the combined filtrates is added 400 cc. of ethyl ether (u. s. p. quality) in order to precipitate inorganic material. After several hours the mixture is filtered, and the residue is washed with a 5 2 mixture of absolute ethyl alcohol and ether. The filtrate is transferred to a 5-1. round-bottomed flask, about 200 cc. of water is added, and the liquids are removed by distillation under reduced pressure. The nearly dry residue is dissolved in 2 1. of water, and the solution is treated with an excess of freshly prepared lead hydroxide (Note 5). The suspension is diluted with water to a volume of about 3.5 1. and is then concentrated under reduced pressure, at as low a temperature as possible, to a volume of about 2 1. The suspension is then filtered with suction (Note 6), and the residue of lead salts is washed thoroughly with water. The cloudy filtrate, which still contains some free ammonia, is concentrated by distillation under reduced pressure to a volume of about 300-400 cc. The mixture is filtered, the filtrate is saturated with hydrogen sulfide gas, and the precipitate of lead sulfide is removed by filtration with suction (Note 6). The solution is now concentrated by distillation under reduced pressure on a water bath, and 1 1. of 95 per cent ethyl alcohol is added to the nearly dry residue of the amino acid. The suspension is boiled under a reflux condenser until nearly all the amino acid is dissolved, and the mixture is then allowed to cool to room temperature. The amino acid, which separates in the form of fine needles, is collected on a Buchner funnel and washed with a little 95 per cent ethyl alcohol. A second crop of... 

The C chemical shifts and some selected C- H spin coupling constants of compound 73 and its hydrochloride are collected in Table 48. The data show a high degree of consistency - in nearly all cases the chemical shifts for carbons of the amino alcohol chain (carbons C-H) are somewhat reduced when switching from the free bases to the hydrochloride salts (the opposite trend is observed for the corresponding H chemical shifts) <2001MOL796>. 

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