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

Participants

Reaction Conditions

Reaction Steps

Methyl acrylate (6.6 L, 73 mol) was charged gradually in three equal portions (each 2.2 L, 24.6 mol) to a mixture of 6-bromo-1-indanone (8.00 kg, 37.9 mol), THF (16 L) and potassium tert-butoxide (210 g, 1.87 mol) at approximately 20-30° C. Additional potassium tert-butoxide (86 g, 0.77 mol), dissolved in THF (0.39 L), was charged after the first portion of methyl acrylate. More potassium tert-butoxide (86 g, 0.77 mol), dissolved in THF (0.39 L), was charged after the second portion of methyl acrylate. Further potassium tert-butoxide (4.64 kg, 41.3 mol) solution in THF (21 L) was then charged gradually at approximately 20-30° C. Solvent (21.5 L) was distilled off at approximately 65° C. and then a mixture of water (49 L) and 50%. aq KOH (2.3 L, mol) was added over approximately 10 min. at below 60° C. The reaction was held at 60° C. for approximately 6 h., then cooled to 20° C. over 1 h. and then filtered after holding at 20° C. for approximately 12 h. The solids were washed with a mixture of water (8 L) and THF (4 L), and then dried to give the title compound (7.47 kg, at 92% w/w NMR assay, 23.4 mol, 62% yield): 1H NMR (500 MHz, DMSO-d6) δ ppm 1.78-1.84 (m, 2 H), 1.95 (td, 2 H), 2.32-2.38 (m, 2 H), 2.51-2.59 (m, 2 H), 3.27 (s, 2 H), 7.60 (d, 1 H), 7.81 (m, 1 H), 7.89 (m, 1 H).

Provenance & Evidence