Hydrochloric Acid → HCID 22890593, compound

Participants

Reaction Steps

DIBAL-H (1.0M solution in hexanes, 8.80 ml, 8.80 mmol) was added dropwise to a stirred solution of 8-4 (2.00 g, 3.52 mmol) in 40 ml of anhydrous THF at −78° C. After 2 hours, the mixture was warmed to room temperature and quenched by slow addition of MeOH (1.6 ml ). A 1.0M aqueous Rochelle salt solution was added, and the mixture was stirred for 30 minutes. EtOAc was added, the organic layer was separated and dried with MgSO4, the solvent was removed under reduced pressure, and the crude product 8-5 was azeotroped with toluene, then dissolved in 40 ml of isopropanol. To the solution was added 3(S)-(6-methoxypyridin-3-yl)-β-alanine tert-butyl ester p-toluenesulfonic acid salt 1-5 (1.73 g, 4.22 mmol), NaOAc (2.89 g, 35.2 mmol), and 3.5 g of powdered molecular sieves. The mixture was stirred at room temperature for 12 hours and was cooled to 0° C., and NaCNBH3 (0.67 g, 10.6 mmol) was added in one portion. The mixture was then warmed to room temperature and stirred for 24 hours. 1H HCl was added to bring the pH to 2. After the mixture was stirred for 10 minutes, EtOAc was added, the pH was then adjusted to 11 with saturated aqueous Na2CO3. The organic portion was separated and dried with MgSO4, filtered, concentrated, and purified by flash silica gel column chromatography (0% to 10% of MeOH in EtOAc).

Provenance & Evidence