Brief introduction of

Reference of 104060-23-3, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 104060-23-3, name is N-Boc-2-(4-Aminophenyl)ethanol belongs to amides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Example 4: Preparation of compounds according to the invention.Diphenylphosphonylated compounds according to the invention (as e.g. in example 2) were prepared according to Scheme 1 , by a fast and convenient synthetic route, affording the opportunity to obtain large and diverse series of compounds. The aminophosphonate building block was prepared from fe/t-butylcarbamate protected 4- aminophenylacetaldehyde (12), prepared from the corresponding alcohol (11) with Dess- Martin periodinane (Dess, D. B. and Martin, J. C. Readily Accessible 12-1-5 Oxidant for the Conversion of Primary and Secondary Alcohols to Aldehydes and Ketones. J. Org. Chem., 1983, 48, 4155-4156.). An amidoalkylation reaction with benzylcarbamate and triphenylphosphite using copper triflate as catalyst, afforded lambda/-benzyloxycarbonyl protected diphenyl phosphonate 13 (Van der Veken, P.; El Sayed, I.; Joossens, J.; Stevens, C. V.; Augustyns, K. and Haemers, A.; Lewis Acid Catalyzed Synthesis of N- Protected Diphenyl 1-Aminoalkyl-Phosphonates. Synthesis, 2005, 4, 634-638). Acidolysis removed the terf-butyl carbamate protecting group. lambda/,lambda/’-bis(te/-butoxycarbonyl)-1- guanylpyrazole was used to introduce the protected guanidine group (Drake, B.; Patek, M.; Lebl, M., A Convenient Preparation of Monosubstituted N,N’-Di(Boc)-Protected Guanidines. Synthesis, 1994, 579-582.). Compound 14 was subsequently deprotected under hydrogenolytic conditions. Small non-peptide guanidyl compounds (7) were made by coupling compound (15) with selected sulfonyl chlorides or acylchlorides in pyridine. EPO The p-acetylaminophenyl phosphonates (as e.g. in example 3) were prepared following scheme 1 using tri-p-acetylaminophenylphosphite (Belyaev et al. A. Structure-Activity Relationship of Diaryl Phosphonate Esters as Potent Irreversible Dipeptidyl Peptidase IV Inhibitors. J.Med. Chem., 1999, 42, 1041-1052) (22).4-(tert-Butyloxycarbonylamino)phenylacetaldehyde (intermediate No. 12 in scheme1 ).Yield: 58%1H NMR (CDCI3, 400MHz) delta 1.5 (s, 9H)1 3.75 (d, 2H), 7.10 (d, 2H), 7.30 (m, 2H), 9.6 (t, 1 H)MS (ESI): m/z (M+Na)258, (M+Me0H+Na) 290Dess-Martin Oxidation: To a stirred suspension of alcohol (1 eq.) in DCM (80ml) at -78 0C, a solution of Dess-Martin periodane (1.5 eq from a 15wt% solution) was added. The suspension was stirred for 3h at room temperature. The resulting solution was poured into a vigorously stirred saturated NaHCO3 and Na2S2O3 solution (1 :1 100ml). The organic layer was separated and washed with brine and dried over Na2SO4. The crude product was obtained by removing the solvent in vacuo.tert-Butyl 4-(2-oxoethyl)phenylcarbamate (12)2-(4-Aminophenyl)ethanol (13.7 g, 0.1 mol) was dissolved in dioxane (120 ml). Triethylamine (10.1 g, 0.1 mol) was added followed by addition of Boc2O (21.8 g, 0.1 mol). The reaction mixture was stirred overnight. After evaporation under vacuum, the residue EPO was dissolved in ethylacetate and washed with HCI (2N) and brine. The organic layer was dried over Na2SO4 and evaporated. Purification by flash chromatography afforded the tert- butyl 4-(2-hydroxyethyl)phenylcarbamate as a white solid (19 g, 80 mmol, 80%). To a stirred solution of this alcohol (1eq) in dichloromethane, a solution of Dess-Martin periodane (1.2 eq from 15% wt solution) was added. The suspension was stirred for 4 h at room temperature. The resulting solution was poured into a vigorously stirred saturated solution of NaHCO3 and Na2S2O3 (1 : 1, 100 ml). The organic layer was separated and washed with brine and dried over anhydrous Na2SO4. This crude aldehyde 12 was used directly for further reaction.

The synthetic route of N-Boc-2-(4-Aminophenyl)ethanol has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UNIVERSITEIT ANTWERPEN; WO2007/45496; (2007); A1;,
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