(S)-N-Boc-3-Bromophenylalanine synthesis
- Product Name:(S)-N-Boc-3-Bromophenylalanine
- CAS Number:82278-73-7
- Molecular formula:C14H18BrNO4
- Molecular Weight:344.2
24424-99-5
82311-69-1
82278-73-7
The general procedure for the synthesis of (S)-3-(3-bromophenyl)-2-((tert-butoxycarbonyl)amino)propionic acid from di-tert-butyl dicarbonate and (S)-2-amino-3-(3-bromophenyl)propionic acid was as follows: first, the reaction was carried out using sodium bicarbonate (3 eq.) and di-tert-butyl dicarbonate (Boc2O, 1.1 eq.) on the (S)-2-amino-3-(3-bromophenyl)propionic acid in a mixed solvent of dioxane and water. -(3-bromophenyl)propionic acid by tert-butoxycarbonyl (Boc) protection reaction to afford the Boc-protected intermediate 7 in 98% yield.Subsequently, the reaction was carried out in dimethylsulfoxide (DMSO) with cuprous iodide (0.4 eq.), cesium carbonate (0.5 eq.), L-proline (0.8 eq.), and sodium salt of methanesulfinic acid (3.9 eq.) as catalysts at 95-100 °C for 9 hours, during which two additional additions of cuprous iodide (0.2 eq.) and L-proline (0.4 eq.) were made, converting the brominated intermediate 7 to the methylsulfoxide-functionalized product 8 in 96% yield. Next, the carboxylic acid group of compound 8 was esterified to a benzyl ester using benzyl alcohol (1.1 eq.), 4-dimethylaminopyridine (DMAP, 0.1 eq.) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC, 1.0 eq.) to give compound 9 in 99% yield. Finally, a Boc deprotection reaction of the amino group was carried out by adding a dioxane solution of 4N HCl to a dichloromethane solution of compound 9 at 0 °C to give the target product 10 in the form of the HCl salt of the free amino group in 94% yield.
24424-99-5
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82311-69-1
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82278-73-7
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Yield:82278-73-7 98%
Reaction Conditions:
with sodium hydrogencarbonate in 1,4-dioxane;water
Steps:
2; 2A; 2B Example 2
[00121] t-Butylcarbamate (Boc) protection of the amino group of bromophenylalaninewas accomplished, using sodium bicarbonate (3 equivalents), t-butyl dicarbonate (Boc2O, 1.1equivalent) in dioxane and water, to obtain compound 7 in 98% yield. A methyl sulfone functionality was introduced by treating the bromo compound 7 with copper iodide (0.4 equivalents), cesium carbonate (0.5 equivalents), L-proline (0.8 equivalents), and the sodium salt of methanesulfinic acid (3.9 equivalents) in dimethylsulfoxide (DMSO) at 95-100°C for a totalof 9 hours, with two further additions of copper iodide (0.2 equivalents) and L-proline (0.4 equivalents) during that period. Compound 8 was isolated in 96% yield. The carboxylic acid of compound 8 was converted to the benzyl ester, compound 9, in 99% yield, using benzyl alcohol (1 .1 equivalent), dimethylaminopyridine (DMAP, 0.1 equivalent) and N-(3 - dimethylaminopropyl)-N-ethylcarbodiimide (EDC, 1.0 equivalent). The amino group ofcompound 9 is deprotected by adding a 4N solution of HC1 in dioxane to compound 9 at 0°C in methylene chloride. The HC1 salt of the free amino species, compound 10 was isolated in 94% yield.
References:
SARCODE BIOSCIENCE INC.;ZELLER, James, Robert;VENKATRAMAN, Sripathy;BROT, Elisabeth, C.A.;IYER, Subashree;HALL, Michael WO2014/18748, 2014, A1 Location in patent:Paragraph 00120; 00121; 00122; 00123; 00124; 00125