Benzylamine → 1-Benzyl-4-methyl-1,4-azaphosphinane 4-oxide

Temperature

0 °C

To a vigorously stirred solution of methylphosphonic dichloride (6.65 g, 50 mmol) in THF (100 mL) at −78° C. was added vinylmagnesium chloride (1.6 M in THF, 66 mL, 105 mmol) dropwisely over 30 min. After the addition is completed, the reaction mixture was warmed to 0° C. over 1 hour, and to it was added benzylamine (6.43 g, 60 mmol) and methanol (100 mL). The reaction mixture was then refluxed for 36 hours. After cooled to room temperature, the reaction mixture was poured into a separation funnel containing saturated aqueous ammonium chloride (100 mL), ethyl acetate (200 mL) and water (100 mL). The organic layer was separated, and the aqueous layer was extracted with methylene chloride (100 mL) twice. The combined organic layer and extracts were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography, eluting with 20% methanol in dichloromethane to give the desired product as white crystalline solid (5.69 g, 51%). LCMS ESI(+) m/z: 224 (M+1).

1. additionAfter the addition
2. temperatureThe reaction mixture was then refluxed for 36 hours
3. temperatureAfter cooled to room temperature
4. additionthe reaction mixture was poured into a separation funnel
5. customThe organic layer was separated
6. extractionthe aqueous layer was extracted with methylene chloride (100 mL) twice
7. dry with materialThe combined organic layer and extracts were dried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by flash chromatography
11. washeluting with 20% methanol in dichloromethane

ORD record

ord-dc8905d3763642f3bbc4290eadcfc9d6

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987284B2