(S)-N-Boc-3-Bromophenylalanine

off-white powder

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 98percent 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 96percent yield. The carboxylic acid of compound 8 was converted to the benzyl ester, compound 9, in 99percent 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 94percent yield.C. (S)-3-(3-Bromo-phenyl)-2-tert-butoxycarbonylamino-propionic acid.; A suspension of 2-amino-3-(3-bromo-phenyl)-N-((2R)-hydroxy-(1R)-methyl-2-phenyl-ethyl)-N-methyl-propionamide (232 mg, 0.593 mmol) in 1 M NaOH (1.2 mL) and water (1.2 mL) was heated at reflux for 2 h and then cooled to rt, whereupon the clear solution became cloudy. Water (10 mL) was added and the solution was extracted with DCM (2.x.). The combined organic layers were washed with water. The aqueous layers were back-extracted with DCM, then combined and concentrated to 5 mL. NaHCO[0200] To a solution of (i -3-(3-bromophenyl)-2-((fer -butoxycarbonyl)amino)propanoic acid (2.00 g, 5.81 mmol) in dichloromethane (15mL) was added EDCI (1.45 g, 7.55 mmol), HOBT (1.02 g, 7.55 mmol), and diisopropylethylamine (2.25 g, 17.43 mmol) at 0C under nitrogen and then 2, 2, 2-trifluoroethan-l -amine.HCl (944.85 mg, 6.97 mmol) was added. The mixture was stirred at 25C for 16 hours. The mixture was poured into water (40 mL) and 1 N hydrochloric acid (10 mL). The mixture was extracted by dichloromethane (40 mL*3). The combined organic phase was washed by saturated sodium carbonate (40 mL*3), brine (20 mL) and dried over sodium sulfate. After filtration and concentration, compound 1-59-1 (2.01 g, 77.1% yield) was obtained as a light yellow solid.

Molecular Weight:344.20
XLogP3:3.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:6
Exact Mass:343.04192
Monoisotopic Mass:343.04192
Topological Polar Surface Area:75.6
Heavy Atom Count:20
Complexity:354
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes