Dichloromethane → (2S)-neopentyl 2-(chloro-(naphthalene-1-yl)phosphorylamino)-propanoate

Participants

Reaction Steps

Naphthalene-1-yl phosphorodichloridate (1219 g, 4.67 mol) and (S)-neopentyl 2-aminopropanoate p-toluenesulfonic acid (1547 g, 4.67 mol) were suspended in anhydrous dichloromethane (15 L) in a 22 L 3-neck flask equipped with a mechanical stirrer, an internal thermocouple, a cooling bath of dry/acetone, an additional funnel and a nitrogen inlet. Anhydrous triethylamine (1.3 L, 9.34 mmol, ≧99.5% grade, Product No 471283, Aldrich) was slowly added at −25° C. for one h. Later the reaction mixture was warmed to room temperature and stirred for overnight and monitored by 31P NMR. After completion, the solvent was removed under reduced pressure and the resulting crude residue that was triturated with a 1:1 mixture of ethyl acetate (2 L)/hexanes (2 L) was filtered by short pad of silica gel (Silicycle, SiliaFlash® P60, 3 inch high, funnel: 3 L medium size) and eluted using a mixture of ethyl acetate/hexanes (3 L: 3 L) followed by rinse with a mixture of ethyl acetate/hexanes (1.5 L: 1.5 L). Upon concentration, the dark oil was diluted with 3 L THF and was concentrated again under reduced pressure to deliver 1700 g (94%) of product which was used without further purification.

Provenance & Evidence