Dimedone → 3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one

To a solution of anti-pyruvic aldehyde-1-oxime (10 g, 1 eq) and 5,5-dimethyl-1,3-cyclohexanedione (16.1 g, 1 eq) in HOAc—H2O (7:3, 200 mL) was added zinc powder (14.95 g, 2 eq) slowly with cooling by a water bath at room temperature. The mixture then was refluxed overnight, concentrated to dryness, partitioned between brine (300 mL) and dichloromethane (300 mL). The pH was adjusted to ca. 6 with saturated aqueous NaHCO3, then the mixture was extracted with dichloromethane (3×200 mL). The organic layers were combined, dried over Na2SO4, filtered, concentrated. The crude product was purified by flash chromatography eluting with 5% ethyl acetate in dichloromethane. The combined organic fractions were concentrated, triturated in ether-hexane (2:1) for 1 hour, then filtered, washed with hexane to give the pure title compound (9 g, 45% yield) as a solid. LCMS m/z: (M+H)=178.1.

1. temperatureThe mixture then was refluxed overnight
2. concentrationconcentrated to dryness
3. custompartitioned between brine (300 mL) and dichloromethane (300 mL)
4. extractionthe mixture was extracted with dichloromethane (3×200 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was purified by flash chromatography
9. washeluting with 5% ethyl acetate in dichloromethane
10. concentrationThe combined organic fractions were concentrated
11. customtriturated in ether-hexane (2:1) for 1 hour
12. filtrationfiltered
13. washwashed with hexane

ORD record

ord-67de33228f5548a4b21328879499c51d

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07358370B2