BOC-D-MEVAL-OH

22838-58-0

74-88-4

13850-91-4

N-(tert-butoxycarbonyl)-D-valine (5 g, 11.5 mmol) was dissolved in THF (69 mL, 0.35 M) at 0 °C, followed by the addition of iodomethane (11.45 mL, 8 eq.). Under stirring, 60% NaH mineral oil dispersion (2.76 g, 3 eq.) was slowly added. The reaction mixture was stirred vigorously at room temperature overnight, after which it was diluted with ether (70 mL) and the reaction was quenched by the slow addition of water (50 mL) at 0 °C. The organic and aqueous layers were separated and the aqueous layer was extracted twice with ether (2 x 30 mL). The pH of the aqueous layer was adjusted to approximately 2 by adding saturated saline dropwise (tested using pH paper), followed by extraction with ethyl acetate (4 × 100 mL). The organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuum. An oily product (4.46 g, 84% yield) was obtained, which was pure enough for the next step of the reaction. For further purification, an analytically pure sample was obtained as a white fluffy solid by fast column chromatography (silica gel, 3%-5% methanol/dichloromethane). When only 3 equivalents of iodomethane were used under similar conditions, a residue of raw material remained at the end of the reaction, probably due to competitive precipitation of the disodium salt.