Phosphorus oxychloride → HCID 21025099, compound

Temperature

75 °C

A 15 mL round bottom flask containing the compound 1C (370 mg, 1.51 mmol) was charged with POCl3 (1 mL) and heated to 75° C. for 2 h. The reaction mixture was concentrated in vacuo and the resulting yellow residue was dissolved in dichloromethane (10 mL) and added, via pipette, to a saturated aqueous solution of NaCHO3 with stirring at 0° C. The heterogeneous mixture was stirred for 10 min at 0° C. then warmed to room temperature and stirred for an additional 1h. The mixture was poured into a separatory funnel and the layers were separated. The aqueous phase was extracted with dichloromethane (2×20 mL) and the combined organic extracts were washed with NaHCO3 (sat. aq., 1×20 mL), dried over Na2SO4, filtered and concentrated in vacuo. The resulting residue was dissolved in EtOAc (20 mL) and filtered through a pad of silica using EtOAc (100 mL) to wash the silica pad. The filtrate was concentrated in vacuo to afford compound 1D as a yellow solid which was used without further purification. HPLC: 100% at 4.160 min (retention time) (YMC S5 ODS column, 4.6×50 mm, eluting with 10-90% aqueous methanol over 4 min containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm).

1. concentrationThe reaction mixture was concentrated in vacuo
2. dissolutionthe resulting yellow residue was dissolved in dichloromethane (10 mL)
3. additionadded, via pipette, to a saturated aqueous solution of NaCHO3
4. stirringThe heterogeneous mixture was stirred for 10 min at 0° C.
5. temperaturethen warmed to room temperature
6. stirringstirred for an additional 1h
7. additionThe mixture was poured into a separatory funnel
8. customthe layers were separated
9. extractionThe aqueous phase was extracted with dichloromethane (2×20 mL)
10. washthe combined organic extracts were washed with NaHCO3 (sat. aq., 1×20 mL)
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. dissolutionThe resulting residue was dissolved in EtOAc (20 mL)
15. filtrationfiltered through a pad of silica
16. washto wash the silica pad
17. concentrationThe filtrate was concentrated in vacuo

ORD record

ord-941de288a1824674a335b48fea8c5450

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07030112B2