반응 #2446106
ord-0c1f528f788649cdba6bf5b76fe44da7
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반응 조건
후처리
- 1온도heated to 90° C. for 10 hr
- 2여과filtered
실험 절차
More specifically, adamantane-1-carboxylic acid (1) (45 g, 0.25 mol) was added to a mixture of AlCl3 (45 g, 0.34 mol) and Br2 (450 g) at 0° C. and stirred at 0-10° C. for 48 hrs, and then kept for 5 hrs at about 20° C. The mixture was then poured onto 500 g crushed ice, diluted with 300 mL of CHCl3 and decolorized with solid Na2S2O5. The aqueous phase was extracted twice with Et2O (50 mL each), and the combined organic phases were washed with H2O and extracted with 10% NaOH. The alkaline extraction was acidified with 2NH2SO4 and kept overnight to provide 49 g (yield=75.7%) of 3-bromoadamantane-1-carboxylic acid (2). Over a course of 0.5 hr, intermediate 2 (16.0 g, 61.7 mmol) in 50 mL of dry chlorobenzene was added at −10° C. to 100 mL of dry chlorobenzene containing 9.3 g (70 mmol) of AlCl3. The mixture was then warmed to room temperature for 1 hr, and then heated to 90° C. for 10 hr. The mixture was then poured onto 200 g of crushed ice and filtered to provide 14.2 g (yield=79.3%) of 3-(4-chlorophenyl)adamantane-1-carboxylic acid (3). Intermediate 3 (1 mmol) was added to a 50 mL round-bottom flask containing HPLC-grade toluene (20 mL), fitted with reflux condenser, and dry N2 was introduced. The mixture was stirred while thionyl chloride (SOCl2) (10 mmol) was added, and refluxed for 1 hr. The sample was then evaporated under a vacuum to produce intermediate 4,3-(4-chlorophenyl)adamantane-1-carbonyl chloride. Without further purification, intermediate 4 was added to 5 mL of a mixture containing 3-hydroxytyramine hydrochloride (5, 1 mmol), NaOH (1 mmol) and Na2CO3 (1 mmol) in 5 mL DMF under N2, and the mixture was stirred at 60° C. for 24 hr and then cool to room temperature. The mixture was evaporated under a vacuum, and 10% HCL was slowly added to the mixture until it reached a pH value of 1. The mixture was then extracted with 20 mL CHCl3, washed three times with water (10 mL each), dried with anhydrous Na2SO4, filtered and concentrated to give Compound 1 as white crystals (yield=83%) with a melting point of 146-148° C. 1H NMR (500 MHz, DMSO) δ 1.63-1.68 (m, 2H, Admant-H), 1.71-1.83 (m, 10H, Admant-H), 2.14 (s, 2H, Admant-H), 2.50-2.53 (m, 2H, CH2), 3.15-3.18 (t, J=7.5 Hz, 2H, NCH2), 3.40 (s, 1H, NH), 6.40-6.42 (d, J=10 Hz, 1H, Ar—H), 6.56 (s, 1H, Ar—H), 6.62-6.63 (d, J=5 Hz, 1H, Ar—H), 7.36-7.41 (m, 4H, Ar—H), 8.68 (s(br), 2H, OH). 13C NMR (500 MHz, DMSO) δ 28.8, 31.3, 35.0, 35.5, 36.3, 36.6, 38.3, 41.0, 41.3, 42.0, 44.3, 115.8, 116.4, 119.8, 127.4, 128.5, 130.7, 131.0, 149.6, 162.9, 176.8. Mass spectroscopy m/z (relative intensity) 426.18 (MH+, 100), 427.18 (68), 428.18 (75).