Sulfuric Acid → HCID 25192133, compound

Cis-4-Aminocyclohexanecarboxylic acid (2.0 g 13.96 mmol) was heated in a flask with a heat gun for 15 minutes. After cooling to room temperature, THF (70 ml) was added followed by lithium aluminum hydride (4 g), slowly and portion wise, and the mixture heated at 65° C. for 1 h. The mixture was cooled, and hexane (70 ml) and sodium hydroxide solution (5 ml) were added whilst rapidly stirring. Celite (5 g) was added and the mixture stirred overnight. The solids were removed by filtration and washed with THF (10 ml). Triethylamine (4 ml) was added followed by a solution of [2,1,3]-benzoxadiazole-5-carbonylchloride (2.0 g, 10.95 mmol) in dichloromethane (15 ml) and the mixture was stirred at room temperature for 0.3 h. Water (100 ml) was added, acidified to pH 2 with sulfuric acid and extracted with ethyl acetate (2×100 ml). The combined organics were washed with saturated sodium bicarbonate solution (100 ml), dried (NaSO4) and evaporated under vacuum. The residue was chromatographed on silica gel eluting with ethyl acetate/dichloromethane/hexane (40:10:50) to give the desired product as a white solid (2.14 g): mp=138-139° C., LC-MS, MH+=258; 1H NMR (300 MHz, CDCl3, rotamers) δ 7.91 (dd, J=1.2 and 9.3 Hz, 1H), 7.90 and 7.83 (dd, J=1.2 and 1.2 Hz, total 1H), 7.51 and 7.46 (dd, J=1.2 and 9.3 Hz, total 1H), 4.58 and 3.42 (br s, total 1H), 3.68-2.64 (m, 2H), 2.12-1.61 ppm (m, 9H).

1. temperatureslowly and portion wise, and the mixture heated at 65° C. for 1 h
2. temperatureThe mixture was cooled
3. additionCelite (5 g) was added
4. stirringthe mixture stirred overnight
5. customThe solids were removed by filtration
6. washwashed with THF (10 ml)
7. additionTriethylamine (4 ml) was added
8. stirringthe mixture was stirred at room temperature for 0.3 h
9. extractionextracted with ethyl acetate (2×100 ml)
10. washThe combined organics were washed with saturated sodium bicarbonate solution (100 ml)
11. dry with materialdried (NaSO4)
12. customevaporated under vacuum
13. customThe residue was chromatographed on silica gel eluting with ethyl acetate/dichloromethane/hexane (40:10:50)

ORD record

ord-f362d57dc87c4d658c24a3393d70991b

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08263591B2