HCID 118201054, compound → Diphenyl N-(1-methyl-2-phenylethyl)phosphoramidate

Temperature

48 °C

A 100 mL, 3-necked flask equipped with an overhead stirrer, reflux condenser and pressure equalizing addition funnel was charged with 2b (10.0 g, 34.6 mmol), THF (50 mL) and CuCl (42 mg, 1 mol %) and the stirrer was started. The stirred mixture was heated to 48° C. and the pressure equalizing addition funnel was charged with PhMgCl (2M in THF, 17.4 mL). This solution was added slowly while maintaining a reaction temperature of 48-51° C. The reaction was allowed to stir at 48-51° C. for an additional 2 hours until the GC analysis indicated the consumption of 2b (<1.0%) and the reaction mixture was cooled to ambient temperature. The reaction was quenched by slow addition to a cooled solution of saturated aqueous ammonium chloride/water mixture (50/50 v/v, 60 mL) while maintaining the batch temperature below 20° C. Heptanes (60 mL) was used to rinse the reactor and was transferred to the quench mixture. The biphasic mixture was agitated for 15 minutes and the aqueous layer was removed. The organic layer washed with deionized water (20 mL) and the organic phase concentrated under reduced pressure to give viscous oil. This residue was dissolved in heptanes (50 mL) and the solution was concentrated under reduced pressure. The residue was crystallized from ethanol (1 g/5 mL) to give 6b as a white solid (9.05 g, 72% yield, 99.85% GC purity containing 0.05% of 8b). Mp 102-103° C. (lit1 101-102° C.). 1H NMR (300 MHz, CDCl3) δ 7.38-7.11 (m, 15H), 3.83-3.65 (m, 1H), 3.00-2.89 (m, 1H), 2.86-2.78 (m, 1H), 2.73-2.62 (m, 1H), 1.15 (d, J=10.1 Hz, 3H).

1. customA 100 mL, 3-necked flask equipped with an overhead stirrer
2. temperaturereflux condenser
3. additionaddition funnel
4. additionaddition funnel
5. additionThis solution was added slowly
6. temperaturewhile maintaining a reaction temperature of 48-51° C
7. customthe consumption of 2b (<1.0%)
8. temperaturethe reaction mixture was cooled to ambient temperature
9. customThe reaction was quenched by slow addition to a cooled solution of saturated aqueous ammonium chloride/water mixture (50/50 v/v, 60 mL)
10. temperaturewhile maintaining the batch temperature below 20° C
11. washto rinse the reactor
12. stirringThe biphasic mixture was agitated for 15 minutes
13. customthe aqueous layer was removed
14. washThe organic layer washed with deionized water (20 mL)
15. concentrationthe organic phase concentrated under reduced pressure
16. customto give viscous oil
17. concentrationthe solution was concentrated under reduced pressure
18. customThe residue was crystallized from ethanol (1 g/5 mL)

ORD record

ord-3e06f485c8924bd88b92b1965ae8319f

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321794B2