Patent GB-804988-A (GB)
Title: 1-phenyl-2-azidoacylamino-1.3-propane diols
Filed: 1956-08-03
Abstract: 1 - Phenyl - and 1 - (p - nitrophenyl) - 2 - azidoacetylaminopropane-1 : 3-diols are produced by contacting an N-azidoacetyl-b -phenylserine derivative of the general formula: <FORM:0804988/IV (b)/1> (wherein X represents H or NO2, R represents H or acyl and R1 represents -O-alkyl, -Cl or N3) with a complex metal hydride in an organic solvent medium at a temperature not substantially exceeding 60 DEG  C.  Preferred reducing agents are alkali and alkaline-earth metal boron and aluminium hydrides, some of which may be prepared in situ from the sodium or potassium compound and an appropriate alkali or alkaline earth metal halide. Examples describe the reduction of racemic or optically active threo-N - azidoacetyl - b  - (p - nitrophenyl) - serine ethyl esters by means of (1) (NaBH4+CaI2) in tetrahydrofuran; (2) Ca(BH4)2-tetrahydrofuran complex in tetrahydrofuran; (3) (NaBH4+LiI.2H2O) in tetrahydrofuran; (4) (NaBH4+CaCl2) in absolute alcohol; (6) (NaBH4+LiCl) in alcohol; (7) (NaBH4+CaI2) in aqueous tetrahydrofuran; (8) LiBH4 in tetrahydrofuran; (9) (NaBH4+BaCl2) in absolute alcohol; (10) (NaBH4+MgCl2) in absolute alcohol; (11) LiAlH4 in ether; (12) NaBH4 in absolute alcohol.  In further examples: (5) DL-threo-N-azidoacetyl-b -phenylserine ethyl ester is reduced by means of (NaBH4+CaI2) in tetrahydrofuran; (13) DL-threo-N-azidoacetyl-b -(p-nitrophenyl)-serine azide is reduced by means of NaBH4 in a mixture of ethyl acetate and water or absolute alcohol; (14) the acid chloride of DL-threo-N-azidoacetyl-O-acetyl-b -(p-nitrophenyl)-serine is reduced by means of KBH4 in aqueous ethyl acetate (or dioxan or diethylene glycol dimethyl ether) and the O-acetyl group is removed by treatment with NaOH in aqueous acetone. Starting materials.  N-Azidoacetyl-b -phenylserine esters of the general formula above (R1=O-alkyl) are prepared by reacting b -phenyl- or b -(p-nitrophenyl)-serine esters, or their functional derivatives modified in the hydroxy or amino group (e.g. acyl compounds or Schiff's bases), with azidoacetic acid or reactive derivatives thereof, or by reacting N-haloacetyl - b  - phenyl - or (p - nitrophenyl) - serine esters, or their functional derivatives modified in the hydroxy group, with alkali or alkaline-earth metal azides If the nitro group is not already present in the starting material, it may be introduced by subsequent nitration, if desired after protecting the hydroxy group.  Details are given of the preparation of the starting materials of the examples as follows: DL - threo - N - azidoacetyl - b  - (p - nitrophenyl)-serine ethyl ester by treating DL-threo-b -(p-nitrophenyl)-serine ethyl ester with azidoacetyl chloride in methylene chloride, if desired in the presence of dimethylaniline, or by similarly acylating DL - threo - b - phenylserine ethyl ester, O-acetylating and nitrating the product and then removing the O-acetyl group, or by reacting DL-threo-b -(p-nitrophenyl)-serine ethyl ester with chloroacetyl chloride in the presence of a base and treating the resulting N-chloroacetyl derivative with sodium azide in aqueous ethanol; DL-threo-N-azidoacetyl - b  - (p - nitrophenyl) - serine azide by reacting the corresponding ethyl ester with hydrazine hydrate in absolute alcohol and treating the resulting hydrazide with sodium nitrite and dilute H2SO4; the acid chloride of DL - threo - N - azidoacetyl - O - acetyl - b  - (p-nitrophenyl)-serine by acetylating DL-threo-N-azidoacetyl - b  - (p - nitrophenyl) - serine and treating the product with thionyl chloride.  Specification 804,986 is referred to.