preparation of cycloheptano[b]pyridine-5,9-dione_industrial additives

preparation background and overview of cyclohepta[b]pyridine-5,9-dione

cycloheptano[b]pyridine-5,9-dione is an organic intermediate. it can be prepared from 2,3-pyridinedicarboxylic acid dimethyl ester and glutarate dimethyl ester as starting materials. prepared by one step reaction.

preparation of cyclohepta[b]pyridine-5,9-dione

preparation step 1 of cyclohepta[b]pyridine-5,9-dione,

to a solution of dimethyl 2,3-pyridinedicarboxylate (750 g, 3.84 mol) and dimethyl glutarate (935 g, 5.84 mol) in toluene (5.25 l) was added potassium tert-butoxide (1.0 m of thf, 9.6 l, 9.6 mol), maintaining the internal temperature <30 °c. the reaction mixture was heated to 55-60°c over 1 hour and held for 1 hour. the reaction mixture was concentrated in vacuo to <7 l and then cooled to 0-5°c. to the concentrated reaction mixture, n-heptane (11.3 l) was added, followed by ice-water (10.9 l), maintaining the internal temperature <5 °c. the ph of the reaction mixture was then adjusted to 6.0-6.5 with glacial acetic acid (435 ml) at 0-5°c. filter the obtained slurry, mica and wash the filter cake with water (2.3 l) and n-heptane (3.7 l) successively, and then dry it under vacuum at 50-55°c to obtain 5,9-dihydroxy-pinacol diborate. 7h-cyclohept[b]pyridine-6,8-dicarboxylic acid dimethyl ester. white solid, yield 822 g, 73%.

preparation step 2 of cyclohepta[b]pyridine-5,9-dione,

dimethyl 5,9-dihydroxy-7h-cyclohept[b]pyridine-6,8-dicarboxylate (610 g, 2.09 mol) in hcl (6.0 n, 3.3 l, 19.8 mol) heat at 75-80°c for 5 hours, then cool to 0-5°c. the ph of the mixture was adjusted to 5.0-5.5 with saturated sodium bicarbonate solution at 0-5°c, and then extracted with dichloromethane (3.0l × 2). the organic phases were combined and filtered through charcoal (300 g) and concentrated in vacuo. the product was crystallized from ethyl acetate (0.75 l) and n-heptane (1.5 l) at 0-5 °c, filtered and dried under vacuum at 40 °c to give 6. cycloheptano[b]pyridine-5,9-dione(6), white crystals, 330 g, 82%. mp = 61.8- 62.6 °c; ¹h nmr ( mhz, cdcl ₃) δ 8.89 (dd, j = 4.6, 1.7 hz, 1h), 8.18 (dd, j = 7.9, 1.6 hz, 1h), 7.56 (dd, j = 7.9, 4.6 hz, 1h ), 2.98 (t, j = 7.0 hz, 2h), 2.92 (dd, j = 7.7, 5.5 hz, 2h), 2.16 (pentet, j = 6.8 hz, 2h); ¹³c nmr (100 mhz, cdcl₃) δ 200.7, 200.4, 154.1, 153.0, 136.8, 133.1, 125.9, 41.8, 41.7, 17.6.

references

[1] from organic letters, 14(18), 4938-4941; 2012