Thionyl Chloride → (2R)-2-((2-(tert-butoxycarbonylamino)ethyl)amino)-3-(2-naphthyl)propionic acid methylester

Participants

Reaction Steps

(2R)-2-Amino-3-(2-naphthyl)propionic acid (5, 0 g, 23 mmol) was added to methanol (150 ml) and thionylchloride (2.0 ml; 23 mmol) was added dropwise and the mixture was stirred overnight and then refluxed for 2.5 h. The solvent was removed in vacuo and the residue was dissolved in a mixture of methanol (95 ml) and acetic acid (5 ml). (2-Oxoethyl)carbamic acid tert-butyl ester (3.4 g, 23 mmol, prepared as in Dueholm et al. Org. Prep. Proced. Int. (1993), 457), sodium cyanoborohydride (1.9 g, 31 mmol) and molecular sieves (50 g, Fluka, 3 Å) were added and the mixture was left overnight. The mixture was filtered and the filtrate was added to water (200 ml) and extracted with methylene chloride (3×100 ml). The combined organic phases were dried (magnesium sulphate), and the solvent was removed in vacuo. The residue was chromatographed on silica (3×30 cm) to afford 3.55 g of (2R)-2-((2-(tert-butoxycarbonylamino)ethyl)amino)-3-(2-naphthyl)propionic acid methylester.

Provenance & Evidence