Hydrochloric Acid → (3-Dibenzylamino-2-hydroxy-5-methyl-hexyl)-phosphonic acid dimethyl ester

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Reaction Conditions

Reaction Steps

Reaction 3: A mixture of the crude oil (3-dibenzylamino-5-methyl-2-oxohexyl)-phosphonic acid dimethyl ester, i.e., compound 3, obtained in reaction 2, was dissolved in about 10% methanol and about 90% THF (v/v) and cooled at −10° C. NaBH4 (68.58 mmol) was added to the mixture in small portions with vigorous stirring. The mixture was stirred at temperature of −10 to 5° C. for 4 h and HCl 5% (v/v) was added. The reaction mixture was concentrated under reduced pressure. The residual oil was dissolved in ethyl acetate, and washed with 30 ml portions of water. The organic phase was dried over anhydrous Na2SO4 and filtered. The solvent was evaporated off to leave (3-dibenzylamino-2-hydroxy-5-methyl-hexyl)-phosphonic acid dimethyl ester as a crude oil. 31P NMR (at 200 MHz, CDCl3) indicated an 80:20 ratio of 2R,3S (δ 34.53) to 2S,3S (δ 35.15) isomers. The diastereomeric mixture was purified by flash chromatography on silica gel using hexane/ethyl acetate as the eluent to afford compound 2R,3S-4 (20.753 g; 64.9% yield; 31P NMR at 200 MHz, CDCl3; δ 34.61).

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