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

Temperature

-2.5 °C

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).

1. customReaction 3
2. customobtained in reaction 2
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. dissolutionThe residual oil was dissolved in ethyl acetate
5. washwashed with 30 ml portions of water
6. dry with materialThe organic phase was dried over anhydrous Na2SO4
7. filtrationfiltered
8. customThe solvent was evaporated off

ORD record

ord-70c3afa9eaa94d319f94f2751d5ea12e

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08178515B2