Phosgene → (R)-3-(4-(isopropylsulfonyl)-3-(pyrrolidin-2-yl)phenyl)-1,1-dimethylurea hydrochloride

Temperatur

0 °C

To 1F (0.25 g, 0.68 mmol) in dichloromethane (5 mL) at 0° C. was added sodium bicarbonate (0.57 g, 6.8 mmol), then phosgene (0.71 mL, 1.36 mmol, 20% in toluene). The reaction was stirred at 0° C. for 30 min. The crude mixture was filtered and washed with dichloromethane. To the filtrate was added triethylamine (0.27 mL, 2.04 mmol), then dimethylamine hydrochloride (0.083 g, 1.02 mmol) and the reaction was stirred for 2 h at rt. The solution was washed with water and brine and dried over sodium sulfate. The solvent was removed and the residue was redissolved in ethyl acetate (2 mL). HCl (4 mL, 4M in dioxane) was added and the reaction was stirred at rt for 4 h. The solvent was removed and dried under high vacuo to give 31A. 1H NMR (400 MHz, Methanol-d4) δ ppm 1.23 (d, J=6.59 Hz, 3H) 1.31-1.40 (m, 3H) 2.14-2.27 (m, 1H) 2.29-2.43 (m, 2H) 2.44-2.60 (m, 1H) 3.02-3.11 (m, 6H) 3.37-3.53 (m, 3H) 5.42 (t, J=7.69 Hz, 1H) 7.64 (dd, J=8.79, 1.76 Hz, 1H) 7.91 (d, J=8.79 Hz, 1H) 8.08 (d, J=2.20 Hz, 1H).

1. filtrationThe crude mixture was filtered
2. washwashed with dichloromethane
3. washThe solution was washed with water and brine
4. dry with materialdried over sodium sulfate
5. customThe solvent was removed
6. dissolutionthe residue was redissolved in ethyl acetate (2 mL)
7. additionHCl (4 mL, 4M in dioxane) was added
8. stirringthe reaction was stirred at rt for 4 h
9. customThe solvent was removed
10. customdried under high vacuo

ORD-Eintrag

ord-4be72812c2574ce490c0298ae69e54e0

Quelldatensatz

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08222453B2