Chloroacetonitrile → HCID 605506, compound

Temperature

10 °C

To a mixture containing 50 g of 5-methoxy-l,3-dimethyloxindole, 10.57 g of Aliquat 366 in 375 ml of toluene and 100 ml of 50% NaOH was added dropwise under nitrogen, a solution containing 21.73 g of chloroacetonitrile in 125 ml of toluene over 30 min. A slightly exothermic reaction ensued (50° C.). The reaction mixture was stirred for another 10 minutes, and then cooled to 10° C. To this cooled reaction mixture was added 400 ml of ice-cold water. The reaction mixture was transferred to a separatory funnel. The layers were separated and the organic layer was extracted with 3N HCl (2×250 ml) and water (1×250 ml). The toluene extract was concentrated under reduced pressure and the resultant dark oil was filtered through silica gel (500 g) eluting with 3% methanol-methylene chloride mixture. The eluate (2 L) was concentrated to give the target compound as an oil (54.61 g; 91% yield) which slowly crystallized upon seeding. This material was sufficiently pure and was reduced to (±)-1,3-dimethyl-5-methoxy-oxindolylethylamine without further purification. A small sample of (±)-cyanomethyl-5-methoxy-1,3-dimethyloxindole was recrystallized from isopropyl ether, m.p.=75.5°-76° C. (lit: 75°-76° C.).

1. customA slightly exothermic reaction ensued (50° C.)
2. customTo this cooled reaction mixture
3. customThe reaction mixture was transferred to a separatory funnel
4. customThe layers were separated
5. extractionthe organic layer was extracted with 3N HCl (2×250 ml) and water (1×250 ml)
6. extractionThe toluene extract
7. concentrationwas concentrated under reduced pressure
8. filtrationthe resultant dark oil was filtered through silica gel (500 g)
9. washeluting with 3% methanol-methylene chloride mixture
10. concentrationThe eluate (2 L) was concentrated

ORD record

ord-05e4fba70063464eb2a64efc71611f08

Source dataset

uspto-grants-1995_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05387695