Methyl iodide → 7'-Bromo-4-methoxy-3',4'-dihydro-1'H-spiro[cyclohexane-1,2'-naphthalen]-1'-one

Temperature

0 °C

7′-Bromo-4-hydroxy-3′,4′-dihydro-1′H-spiro[cyclohexane-1,2′-naphthalen]-1′-one (Intermediate 8, 1.78 g, 5.76 mmol) was dissolved in 2-methyl THF (15 mL) under an inert atmosphere and the solution was cooled to 0° C. Methyl iodide (0.720 mL, 11.5 mmol) was added followed by portion wise addition of potassium tert-butoxide (1.29 g, 11.5 mmol). The resulting mixture was stirred at r.t. overnight. Potassium tert-butoxide (0.323 g, 2.88 mmol) and methyl iodide (0.717 mL, 11.5 mmol) were added. The mixture was stirred for 1.5 h. Potassium tert-butoxide (0.194 g, 1.73 mmol) was added and the mixture was stirred for an additional 2 h. Brine was added and the phases were separated. The aqueous phase was extracted with EtOAc and to the combined organics were added activated charcoal. The mixture was filtered through a pad of diatomaceous earth and rinsed with EtOAc. The organic phase was concentrated in vacuo to give the title compound (1.41 g, 76% yield): MS (ES+) m/z 323 [M+H]+.

1. stirringThe mixture was stirred for 1.5 h
2. stirringthe mixture was stirred for an additional 2 h
3. customthe phases were separated
4. extractionThe aqueous phase was extracted with EtOAc
5. additionto the combined organics were added
6. filtrationThe mixture was filtered through a pad of diatomaceous earth
7. washrinsed with EtOAc
8. concentrationThe organic phase was concentrated in vacuo

ORD record

ord-51276f974c2f46f2838b6963026c12df

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09000184B2