Acetamide, hydrolysis reduction

In a different approach a super-high-throughput ee-assay was developed on the basis of chirally modified capillary array electrophoresis (CAE).90 CAE was used in the Human Genome Project, and commercially available instruments have been developed which comprise a high number of capillaries in parallel, for example the 96-capillary unit MegaBACE consisting of 6 bundles of 16 capillaries.91 The system can address a 96-well microtiter plate. It was adapted to perform ee-determinations of chiral amines, which are potentially accessible by catalytic reductive amination of ketones, transition metal catalyzed Markovnikov addition of ammonia, or enzymatic hydrolysis of acetamides (Scheme 14).90... 

Chlorophenyl)glutarate monoethyl ester 87 was reduced to hydroxy acid and subsequently cyclized to afford lactone 88. This was further submitted to reduction with diisobutylaluminium hydride to provide lactol followed by Homer-Emmons reaction, which resulted in the formation of hydroxy ester product 89 in good yield. The alcohol was protected as silyl ether and the double bond in 89 was reduced with magnesium powder in methanol to provide methyl ester 90. The hydrolysis to the acid and condensation of the acid chloride with Evans s chiral auxiliary provided product 91, which was further converted to titanium enolate on reaction with TiCI. This was submitted to enolate-imine condensation in the presence of amine to afford 92. The silylation of the 92 with N, O-bis(trimethylsilyl) acetamide followed by treatment with tetrabutylammonium fluoride resulted in cyclization to form the azetidin-2-one ring and subsequently hydrolysis provided 93. This product was converted to bromide analog, which on treatment with LDA underwent intramolecular cyclization to afford the cholesterol absorption inhibitor spiro-(3-lactam (+)-SCH 54016 94. 

The synthetic route began with the synthesis of the bromide 147 by benzylation and ketalisation of the known aldehyde 146 (Scheme 20). Generation of the Grignard reagent followed by addition of chiral oxazoline 105 afforded the biaryls 148 and 149 in 64% yield and a ratio of 77 23 respectively along with 22% of the demethylated oxazoline 114. Quaterisation, base hydrolysis and reduction then gave the alcohol 150 which was converted into the acetamide 144 by... 

Of Neoproaporphines. Oxidation of norprotosinomenine trifluor-acetamide with vanadium oxytrifluoride gave the phenolic neoproaporphine 11. Alkaline hydrolysis and bond cleavage, followed by borohydride reduction of the imine bond, supplied the dibenzazonine base 12 in good yield. ... 

Transformation of oxazoline 53 formed the amino alcohol derivatives 54 on opening of the ring with H2SO4. Reduction of 53 with diisobutylaluminium hydride provided A -Ethyl amino alcohol 55. Oxazoline was converted to acetamide 56 by acidic hydrolysis with trifluoroacetic acid. The overall transformation of 53 to 56 represents the regioselective caibohydroxylation of (V-Allylacetamide [83-84] (Scheme 12.13). 

The Leuckart reaction (reductive amination of carbonyl compounds with formamide and formic acid) of 2-norbornanone and (lR)-(V-(3,3-dimethyl-2-oxo-l-norbornyl) acetamide furnishes the expected A-(2-norbornyl)formamides. (l/()-AI-(7,7-Dimethyl-2-0X0-l-norbornyl)acetamide, on the other hand, gives a product resulting from a Wagner-Meerwein rearrangement of the usual cationic intermediate followed by an unprecedented transamination, which affords an A,A-diacylammonium ion. Hydrolysis gives (15 )-A-(3,3-dimethyl-2-oxo-l-norbornyl)acetamide, which then undergoes the normal Leuckart reaction. 

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