Methyl Acrylate → 6'-(3-Fluoropropoxy)spiro[cyclohexane-1,2'-indene]-1',4(3'H)-dione

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-(3-fluoropropoxy)-2,3-dihydro-1H-inden-1-one (Intermediate 62, 3.42 g, 16.4 mmol) and methyl acrylate (3.26 mL, 36.1 mmol) in 2-Me THF (15 mL) was cooled to 0° C. Potassium tert-butoxide (2.21 g, 19.71 mmol) was added in portions. After stirring for 1 h at r.t., water (22.5 mL) and KOH (0.921 g, 16.4 mmol) were added and the mixture was heated at reflux for 4.5 h. The mixture was allowed to cool to r.t. and brine was added. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to yield 3.14 g (66% yield) of the title compound which was used in the next step without further purification: 1H NMR (400 MHz, CDCl3) δ 1.82-1.91 (m, 2H), 2.13-2.27 (m, 4H), 2.41-2.52 (m, 2H), 2.70 (dt, 2H), 3.16 (s, 2H), 4.11-4.17 (m, 2H), 4.60 (t, 1H), 4.72 (t, 1H), 7.21-7.27 (m, 2H), 7.39 (dd, 1H); MS (ES+) m/z 291 [M+H]+.

Provenance & Evidence