Synthesis of enantiomerically pure phosphonic analog of natural aspartic acid

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Methyl ester of L-serine I was Boc-protected at the NH-group [1], then the obtained (S)-hydroxyaminocarboxylate II was transformed into bromide (R)-III through reaction with triphenylphosphine and trichlorobromomethane in methylene chloride at 70°С. Bromide III was purified by vacuum distillation and brought into the Arbuzov reaction with five-fold excess of triethyl phosphite, the reaction proceeded at 135–140°С over 12 h. After distilling off the volatile reaction product at 0.1 mm Hg at 120°С, the phosphonate IV was obtained, which was purified by column chromatography. Its structure was proved by the Н, С and Р NMR spectroscopy and mass spectrometry. The heating of compound IV with hydrochloric acid affords (R)-(+)-С-phosphonoaspartic acid V. This compound have been earlier obtained by a more complicated method [2]. The physical properties and optical rotation angle coincided with the published data. Methyl (S)-tert-buthoxycarbonylamino-3-hydroxypropionate (II). To a solution of 10.5 g (0.05 mol) of (S)-methyl serinate hydrochloride in 10 ml of THF was added 15 g of triethylamine at 0°С and this mixture was stirred for 30 min. Then 12 g of Boc2O was added, and the reaction mixture was warmed to room temperature, stirred for 6 h, and then refluxed for 3 h. Then it was cooled, poured into the saturated aqueous sodium hydrogen bicarbonate solution, extracted with diethyl ether, and concentrated. Yield 90%, [α]D 18.0 (MeOH, c 5), colorless oil. Н NMR spectrum (CDCl3), δ, ppm: 1.44 s [9H, (CH3)3C], 3.77 s (3H, CH3O), 3.9 m (2H, CH2), 4.38 m (1H, CHN), 5.57 br.s (1H, NH).