Sulfuric Acid → HCID 66665903, compound

To a solution of (R)-5-difluoromethyl-5-(2-fluoro-phenyl)-morpholin-3-one (120 g, 489.4 mmol) in CH2Cl2 (1.2 L) was added P2S5 (108 g, 489.4 mmol) at room temperature. The resulted yellow suspension was heated to reflux for 3.5 h. The reaction mixture was filtered through a pad of silica gel (200˜300 mesh), washed with CH2Cl2 for 3 times to get a brown solution. The solvent was removed to provide the crude product as an orange solid, which was dispersed in THF (100 mL), then 25% NH3 water solution (750 mL) was added at room temperature. 27 hours later, the reaction mixture was extracted with IPAC. The combined organic phase was washed with water, concentrated to provide a yellow oil. The crude product was dissolved in IPAC (1.2 L) and MeOH (60 mL) and some solid undissolved was removed through filtration. Then conc. H2SO4 (57.6 g, 587.3 mmol) was added to get a white suspension. The suspension was stirred at room temperature overnight and filtered to provide the title compound as a white solid: ESIMS: 245; [(M−H2SO4+H)+]; 1H NMR (400 MHz, DMSO-d6): δ 9.60 (bs, 1H), 8.82 (br s, 1H), 7.52 (m, 2H), 7.35 (m, 2H), 6.75 (t, 1H), 4.65 (dd, 2H), 4.36 (d, 1H), 4.14 (d, 1H).

1. temperatureThe resulted yellow suspension was heated
2. temperatureto reflux for 3.5 h
3. filtrationThe reaction mixture was filtered through a pad of silica gel (200˜300 mesh)
4. washwashed with CH2Cl2 for 3 times
5. customto get a brown solution
6. customThe solvent was removed
7. customto provide the crude product as an orange solid, which
8. extraction27 hours later, the reaction mixture was extracted with IPAC
9. washThe combined organic phase was washed with water
10. concentrationconcentrated
11. customto provide a yellow oil
12. customsome solid undissolved was removed through filtration
13. customto get a white suspension
14. filtrationfiltered

ORD record

ord-6962e091471d403da4264e62c2c1942e

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08338413B1