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

Participants

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 (19.05 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 10 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, compound 4, 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. (3-Dibenzylamino-2-hydroxy-5-methyl-hexyl)-phosphonic acid dimethyl ester can be isolated by chromatography or used in the next hydrogenolysis step directly without isolation.

Provenance & Evidence