Pyridine → (4R)-(+)-(4-pyridyl)-2-(4-nitrophenoxy)-2-oxo-1,3,2-dioxaphosphorinane

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 4-nitrophenyl phosphorodichloridate (9.2 g, 36 mmol) in THF (100 mL) at 0° C. was slowly added pyridine (7.9 mL, 98 mmol) over 30 minutes. The reaction mixture was stirred for 5 minutes at 0° C. and slowly added to a solution of R-(+)-1-(4-pyridyl)-1,3-propane diol 95.8% ee, 5 g, 32.7 mmol) and triethylamine (15.6 mL, 114 mmol) in THF (300 mL) at 0° C. over 1.5 hours. The reaction mixture was allowed to warm to room temperature and stirred for 2.5 hours. Sodium 4-nitrophenoxide (18.17 g, 131 mmol) was added and the heterogeneous orange reaction mixture was heated at 40° C. for 4.5 hours. The reaction mixture was cooled to 0° C., quenched with a saturated aqueous solution of ammonium chloride (250 mL) and the layers were separated. The organics were washed with a saturated aqueous solution of ammonium chloride (200 mL) and the combined aqueous washes were back-extracted with dichloromethane (100 mL). The combined organic extracts were washed with a 0.3 N aqueous solution of sodium, hydroxide (200 mL×4) and dried over magnesium sulfate. The filtered solution was concentrated under reduced pressure to give an oil that crystallized upon standing. The yellow solid was recrystallized from 100 mL of 2-propanol to afford the desired trans-phosphate (12) as a white solid (95% ee, [α]D20+74.2 (c 1.0, MeOH)).

Provenance & Evidence