Methyl vinyl ketone → HCID 57603342, Verbindung

To a solution of 6-chloro-2-(2-fluoroethyl)-5-methoxyindan-1-one (34 g, 140 mmol) in toluene (1500 mL) was added N-[4-(trifluoromethyl)benzyl]cinchoninium bromide (13 g, 24 mmol) and the mixture was stirred at room temperature for 30 minutes. After cooling to 0° C., methyl vinyl ketone (20 mL, 240 mmol) was added followed by potassium hydroxide pellets (85%, 34 g, ˜52 mmol) and the mixture was vigorously stirred for 90 minutes. The reaction mixture was diluted with dichloromethane (1000 mL), dried with MgSO4 and filtered. The filtrate was filtered through a pad of silica gel, washing with Et2O and EtOAc. The filtrate was concentrated under reduced pressure and the residue was chromatographed on silica gel (elution with 30% to 50% EtOAc/hexanes) to give 6-chloro-2-(2-fluoroethyl)-5-methoxy-2-(3-oxobutyl)indan-1-one as a yellow oil. Analysis by chiral HPLC indicated an enantiomeric ratio of approximately 2:1 favoring the desired (2S)-enantiomer. This enantiomerically enriched material was utilized for the remainder of the synthesis.

1. temperatureAfter cooling to 0° C.
2. stirringthe mixture was vigorously stirred for 90 minutes
3. dry with materialdried with MgSO4
4. filtrationfiltered
5. filtrationThe filtrate was filtered through a pad of silica gel
6. washwashing with Et2O and EtOAc
7. concentrationThe filtrate was concentrated under reduced pressure
8. customthe residue was chromatographed on silica gel (elution with 30% to 50% EtOAc/hexanes)

ORD-Eintrag

ord-f12c02abede045b4a394a338e1895f98

Quelldatensatz

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07923568B2