(S)-N-Boc-3-Bromophenylalanine Chemical Properties

Melting point:

106.1°C

Boiling point:

475.3±40.0 °C(Predicted)

Density 

1.5311 (rough estimate)

refractive index 

1.6500 (estimate)

storage temp. 

Sealed in dry,Room Temperature

pka

3.81±0.10(Predicted)

form 

Solid

color 

White to off-white

optical activity

Consistent with structure

Water Solubility 

Slightly soluble in water.

InChI

InChI=1S/C14H18BrNO4/c1-14(2,3)20-13(19)16-11(12(17)18)8-9-5-4-6-10(15)7-9/h4-7,11H,8H2,1-3H3,(H,16,19)(H,17,18)/t11-/m0/s1

InChIKey

FBUDYESOPLBQIR-NSHDSACASA-N

SMILES

C(O)(=O)[C@H](CC1=CC=CC(Br)=C1)NC(OC(C)(C)C)=O

CAS DataBase Reference

82278-73-7(CAS DataBase Reference)

Safety Information

HazardClass 

IRRITANT

HS Code 

2922498590

(S)-N-Boc-3-Bromophenylalanine Usage And Synthesis

Chemical Properties

off-white powder

Uses

N-Boc-3-bromo-L-phenylalanine is used as pharmaceutical intermediate.

Synthesis

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.

References

[1] ACS Medicinal Chemistry Letters, 2012, vol. 3, # 3, p. 203 - 206
[2] Patent: WO2014/18748, 2014, A1. Location in patent: Paragraph 00120; 00121; 00122; 00123; 00124; 00125
[3] Catalysis Science and Technology, 2016, vol. 6, # 12, p. 4086 - 4089
[4] Patent: WO2009/102876, 2009, A1. Location in patent: Page/Page column 56

(S)-N-Boc-3-Bromophenylalanine(82278-73-7)Related Product Information

• L-Alanine
• DL-Phenylalanine
• 3-Bromofluorobenzene
• Phenprobamate
• 2-Bromobenzaldehyde
• Bromoxynil octanoate
• 1,4-Dibromobenzene
• 1,2-Dibromobenzene
• Bromoxynil
• 4-Bromobenzaldehyde
• N-(tert-Butoxycarbonyl)-L-phenylalanine
• D-Phenylalanine
• EC 2.6.1.2
• D-Alanine
• L-Phenylalanine
• DI-TERT-BUTYL ETHER
• 1-Bromo-4-nitrobenzene
• Boc-(S)-4-Bromophenylalanine