8-Methoxyquinoline

(0.3 mmol, 48 mg), Tetrahydroxy diboron (0.9mmol, 81mg), Cu (OAc) 2 (0.015 mmol, 2.5 mg) was added to 1 mL of acetonitrile, 40 C for 12 hours, Purification by thin layer chromatography gave 44.5 mg of 8-methoxytetrahydroquinoline in a yield of 91% with a purity of 98%General procedure: A 20 mL Schlenk tube was charged with quinoline (1a; 65 mg, 0.5 mmol), Cu(OAc)2 (4.5 mg, 0.025 mmol), B2(OH)4 (135 mg, 1.5 mmol), and MeCN (2.0 mL). The mixture was stirred at 40 C for 8 h until the reaction was completed (TLC), then cooled to room temperature and concentrated under reduced pressure. Water (10 mL) was added and the mixture was extracted with EtOAc (3 x 10 mL). The organic phases were combined, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography with petroleum ether/ethyl acetate (8:1) as an eluent to give a brown liquid (2a: 65 mg, 98% yield).Step B - Synthesis of Compound Int- 19b; A solution of compound Int- 19a (21 g, 0.132 mol) and Pt02 (2 g, 5 mol %) in 80 mL of MeOH was allowed to stir at room temperature for 4 hours under a H2 atmosphere (40 psi). The reaction mixture was filtered and the filtrate was concentrated in vacuo to provide compound Int-19b as yellow oil (18 g, 84%). NMR: (CDC13) delta 6.57-6.64 (m, 3H), 4.25 (br, 1 H), 3.84 (s, 3H), 3.35 (s, 2H), 2.79-2.80 (m, 2H), 1.96-1.99 (m, 2H).Step B - Synthesis of Compound Int-19bInt 9a Int 19bA solution of compound Int-19a (21 g, 0.132 mol) and Pt02 (2 g, 5 mol %) in 80 mL of MeOH was allowed to stir at room temperature for 4 hours under a H2 atmosphere (40 psi). The reaction mixture was filtered and the filtrate was concentrated in vacuo to providecompound Int-19b as yellow oil (18 g, 84%). 1H MR: (CDC13) delta 6.57-6.64 (m, 3H), 4.25 (br, 1H), 3.84 (s, 3H), 3.35 (s, 2H), 2.79-2.80 (m, 2H), 1.96-1.99 (m, 2H).To a dry vial containing Add sodium cyanoborohydride (505 g, 8.1 1 mol) in EtOH (1 L) to a solution of 8- methoxy quinoline (425 g, 2.673 mol) in EtOH (9 L), and stir. Cool the reaction mixture to an internal temperature of 0 C and add HC1 (35%, 1.12 L, 10.962 mol) dropwise over 60 min so that the internal temperature did not rise above 20 C. Allow the reaction mixture to warm to ambient temperature and then heat to reflux for 2.5 hours. Cool to ambient temperature and stir overnight. Add ammonium hydroxide (25%, 1 L); dilute with water (15 L); and extract the mixture with dichloromethane (3 x 10 L). Combine the organic layers and dry over sodium sulfate. Remove the solids by filtration. Collect the filtrate and concentrate under reduced pressure to give a residue. Purify the residue by silica gel flash chromatography, eluting with ethyl acetate: hexane (1: 10) to give the title compound (357 g, 82%). ESI (m/z) 164(M+H).General procedure: Appropriate RI (R CH3, Et, CH2CH]CH2, Bui ) (1.20 mol) wasadded to the 1a or 1b (0.60 mol) at room temperature. After thecompletion of addition, the reaction mixture was heated underreflux for 16 h. The excess of RI was slowly evaporated at roomtemperature. The crude product was purified by crystallizationfrom ethanol (or methanol) and dried over P4O10 to yield precipitatesas follows:

Molecular Weight:159.18
XLogP3:1.8
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:159.068413911
Monoisotopic Mass:159.068413911
Topological Polar Surface Area:22.1
Heavy Atom Count:12
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes