Phosphorodichloridic acid, phenyl ester → HCID 86693901, compound

1-Butanol (1200 mL) was cooled to −20° C. and 50 mL of SOCl2 added with stirring followed by 50 g (33.67 mmol) of (S)-2-aminopropanoic acid. The solution was heated 24 hrs at reflux, most of the solvent stripped off, and the residue was dissolved in 800 mL of diethyl ether. The mixture was left for 1 hr at 0° C. to afford (S)-butyl 2-aminopropanoate hydrochloride (intermediate 11.47 g). Phenyl phosphorodichloridate (48.9 g, 232 mmol) and (S)-butyl 2-aminopropanoate hydrochloride (42 g, 232 mmol) were suspended in anhydrous CH2Cl2 (200 mL). N,N-diisopropylethylamine (59.9 g, 464 mmol) was added drop wise at −78° C., and after 4 hrs the reaction was concentrated. Diethylether (Et2O, 500 mL) was added and the resulting precipitate was filtered off and washed with dry Et2O (twice 100 mL). The filtrate was evaporated to dryness. (2S)-butyl 2-(chloro(phenoxy)phosphorylamino)propanoate (12) was stored as 0.5 M solution in THF at −18° C. until further reaction.

1. concentrationafter 4 hrs the reaction was concentrated
2. additionDiethylether (Et2O, 500 mL) was added
3. filtrationthe resulting precipitate was filtered off
4. washwashed with dry Et2O (twice 100 mL)
5. customThe filtrate was evaporated to dryness
6. custom(2S)-butyl 2-(chloro(phenoxy)phosphorylamino)propanoate (12) was stored as 0.5 M solution in THF at −18° C. until further reaction

ORD record

ord-bfed9a8276ea457791cee6a45b696e2b

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09006209B2