Patent GB-762240-A (GB)
Title: Process for the manufacture of n-acylated amino-alcohols
Filed: 1954-06-25
Abstract: N-Acylated aminoalcohols are manufactured by reducing an N-acylated aminoacid azide with a complex metal hydride.  The process is particularly applicable to the reduction of N-acylated monobasic hydroxymonoaminoacids containing in the b -position an aryl radical which may be substituted (e.g. by a nitro group, a chlorine atom or an alkoxy or alkylmercapto group in the 2- or 4-position), especially those containing a 4-nitroaryl group and substituted in the amino group by an aliphatic acyl radical of at most 5 carbon atoms or by a dichloroacyl radical.  In examples: (1) threo-N-acetyl-b -phenylserine azide in ethyl acetate is reduced with sodium boron hydride in methanol to threo-1-phenyl-2-acetylaminopropanediol-1 : 3, which is heated with acetic anhydride to form the O1 : N-diacetyl compound; (2) threo-N-acetyl-b -(p-chlorophenyl)-serine azide is similarly reduced to threo-1-(p - chlorophenyl) - 2 - acetylaminopropanediol-1 : 3; (3) threo-N-acetyl-b -phenyl-b -methoxy-a -aminopropionic acid azide in ethyl acetate is reduced with sodium boron hydride in ethanol and the product is hydrolysed and reacylated with benzoyl chloride to give threo-1 - phenyl - 1 - methoxy - 2 - benzoylamino-propanol - 3; (4) threo - N - acetyl - b - (p-nitrophenyl) - b  - methoxy - a  - aminopropionic acid azide is reduced as in (1) to threo-1-(p-nitrophenyl) - 1 - methoxy - 2 - acetylaminopropanol - 3; (5) N - acetylphenylalanine azide is similarly reduced and the product heated with acetic anhydride to form 1-phenyl-2-acetylamino-3- acetoxypropane; (6) N-acetyl - p - nitrophenylalanine azide similarly yields 1 - (p - nitrophenyl) - 2 - acetylamino-3 - acetoxypropane; (7) N - benzoyl - g  - amino-butyric acid azide is reduced as in (1) to 4-benzoylaminobutanol - 1; (8) threo - N - acetyl-b  - (p - phenylphenyl) - serine azide similarly yields threo - 1 - (p - phenylphenyl) - 2 - acetyl-aminopropanediol - 1 : 3; (9) N - acetyl-b  - (p - chlorophenyl) - b  - aminopropionic acid azide is treated as in (5) to produce 1-(p-chlorophenyl) - 1 - acetylamino - 3 - acetoxypropane; (10) N - acetyl - b  - (o - nitrophenyl) - b  - aminopropionic acid azide similarly yields 1-(o-nitrophenyl) - 2 - acetylamino - 3 - acetoxypropane; (11) DL - threo - b  - (p - nitrophenyl) - N - dichloroacetylserine azide in a mixture of ether and ethyl acetate is reduced with sodium boron hydride in methanol to DL-threo-1-(p-nitrophenyl) - 2 - dichloracetylaminopropanediol-1 : 3; (12) the same reduction is effected by means of lithium aluminium hydride in ether; (13) L(+)-threo-b -(p-nitrophenyl)-N-dichloracetylserine azide in ethyl acetate is reduced with sodium boron hydride in water to chloramphenicol.  Starting materials.  Amino-acid azides are obtainable by reacting the corresponding acid halides with alkali metal azides or by converting amino-acid esters to hydrazides (e.g. by reaction with hydrazine hydrate in an inert solvent), and treating the hydrazides (which need not be purified) with nitrous acid (which may be liberated from a salt thereof), advantageously while cooling well.  Reactive substituents such as hydroxy groups may be protected by acylation.  The preparation of the starting materials of the examples is described in detail. Threo-N-acetyl-b -(p-phenylphenyl)-serine methyl ester (from which the starting material of Example (8) is prepared) is produced by reacting p-phenylbenzaldehyde with amino acetic acid, and esterifying and acetylating the resulting threo-b -(p-phenylphenyl)-serine.