Acetic Acid → 5-Dimethylaminophthalide

Temperature

0 °C

To a stirred suspension of 5-aminophthalide (5.00 g, 33.5 mmol) in acetonitrile (120 ml), was added 37% formaldehyde aqueous solution (24.9 ml, 335 mmol) and sodium cyanoborohydride (8.42 g, 134 mmol). The mixture was cooled to 0° C., followed by addition of 10% AcOH aqueous solution (120 ml). The mixture was warmed to room temperature from 0° C. during 1.5 hour-period. The mixture was concentrated under reduced pressure to a smaller volume and was extracted with EtOAc (2×125 ml). The combined organic layers were washed with saturated NaHCO3 solution (125 ml) and brine (125 ml), dried over Na2SO4. Removal of the solvent produced a crude product. Recrystallization of the crude product from MeOH gave 5-dimethylamino-3H-isobenzofuran-1-one as an off-white solid (3.90 g, 66%).

1. temperatureThe mixture was warmed to room temperature from 0° C. during 1.5 hour-period
2. concentrationThe mixture was concentrated under reduced pressure to a smaller volume
3. extractionwas extracted with EtOAc (2×125 ml)
4. washThe combined organic layers were washed with saturated NaHCO3 solution (125 ml) and brine (125 ml)
5. dry with materialdried over Na2SO4
6. customRemoval of the solvent
7. customproduced a crude product
8. customRecrystallization of the crude product from MeOH

ORD record

ord-5de2b5014ded4b3cb5aa1240bb63f239

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07060844B2