Dimethyl Sulfoxide → HCID 14804749, compound

Temperature

-78 °C

Trifluoroacetic anhydride (30 ml, 44 g, 212 mmol) in dry dichlcromethane (100 ml) was added dropwise over 15 min to a stirred solution of dimethylsulphoxide (16 ml, 17.6 g, 259 mmol) in dry dichloromethane (500 ml) at -78° C. under nitrogen. After a further 10 min 1-benzyloxy-3-hydroxy-4-methylpyrrolidin-2-one (10 g, 45 mmol) in dichloromethane (80 ml) was added via cannula to the cloudy solution. After 30 min diisopropylethylamine (56 ml, 42 g, 330 mmol) was added dropwise over 5 min, and the reaction stirred for a further 35 min at -78° C. before being quenched at that temperature by the addition of methanol (20 ml). The mixture was then warmed to 0° C., washed with water (300 ml), and the water back extracted twice with dichloromethane. The combined organic layers were washed with brine, the brine extracted with dichloromethane, and the combined dichloromethane layers dried (Mg2SO4). After evaporation the product was purified by flash chromatography, eluting with dichloromethane: methanol (98:2 v/v) to give 1-benzyloxy-4-methylpyrrolidin-2,3-dione (7.8 g, 78%) as a white solid. In CDCl3 solution the ketone exists in its enol tautomeric form. 1H NMR (360 MHz, CDCl3) δ7.3-7.5 (5 H, m, Ph), 5.01 (2 H, s, OCH2), 3.61 (2 H, q, J=0.9 Hz, NCH2), 1.81 (3 H, t, J=0.9 Hz, CH3), m/z (CI, isobutane) 220 (M+ +H).

1. custombefore being quenched at that temperature by the addition of methanol (20 ml)
2. temperatureThe mixture was then warmed to 0° C.
3. washwashed with water (300 ml)
4. extractionthe water back extracted twice with dichloromethane
5. washThe combined organic layers were washed with brine
6. extractionthe brine extracted with dichloromethane
7. dry with materialthe combined dichloromethane layers dried (Mg2SO4)
8. customAfter evaporation the product
9. customwas purified by flash chromatography
10. washeluting with dichloromethane: methanol (98:2 v/v)

ORD record

ord-2b90968895eb4ff7bbf5ffdc8880d9b6

Source dataset

uspto-grants-1990_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04925867