Hydrochloric Acid → HCID 97107398, compound

Participants

Reaction Conditions

Reaction Steps

Sodium borohydride (15.5 g, 410 mmol) was dissolved in THF, and the solution was chilled to 0° C. Boron trifluoride etherate (52.3 mL, 424 mmol) was added to the solution and the mixture was allowed to warm to rt and stirred for 30 min. Then a solution of tert-butyl 4-(4-(benzyloxy)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (50 g, 137 mmol, intermediate A) in 500 mL of THF was added and the reaction mixture was stirred for 2 h at rt. A 100 mL portion of water was then added slowly to the mixture (Caution: effervescence is observed). The mixture was diluted with 100 mL of ethanol, and sodium hydroxide (228 mL, 10% solution in water, 0.684 mol) and hydrogen peroxide (20.5 mL, 0.684 mol) were added. The reaction mixture was heated to reflux temperature and stirred for 16 h. The mixture was cooled to 10° C. and diluted with 1 L of DCM. Then the pH was adjusted to 7 with 1.5 L of 1.5 N HCl. The layers were then separated, and the aqueous layer was extracted with an addition two 500 mL portions of DCM. The organic layers were combined, washed with 2×1 L of water and 200 mL of brine, dried over sodium sulfate, and evaporated in vacuo to provide an off-white solid. The solid was triturated with 500 mL of pet ether, and isolated by filtration to yield 46.5 grams of product (88%, 99.0% purity by HPLC). LC/MS RT (conditions A)=2.372 min, (M+H)+=382.0. 1H NMR (400 MHz, DMSO-d6) δ 7.47-7.42 (m, 2H), 7.42-7.36 (m, 2H), 7.36-7.28 (m, 1H), 7.14 (d, J=9.0 Hz, 2H), 6.92 (d, J=9.0 Hz, 2H), 5.07 (s, 2H), 4.74 (d, J=5.5 Hz, 1H), 4.10 (br. s., 1H), 3.94 (br. s., 1H), 3.46-3.35 (m, 1H), 2.47-2.31 (m, 2H), 1.70-1.61 (m, 1H), 1.55-1.45 (m, 2H), 1.42 (s, 9H).

Provenance & Evidence