Oxalyl chloride → HCID 59255047, Verbindung

To a solution of 5-chloro-1-isopropyl-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid as prepared in Example 1(7) (2.66 g, 11.6 mmol) in dichloromethane (30 mL) were added oxalyl chloride (4.41 g, 34.8 mmol) and a drop of N,N-dimethylformamide at room temperature, and the mixture was stirred at room temperature for 2 h. The solvent and excess amounts of oxalyl chloride were removed in vacuo. The residue was dissolved in dichloromethane (80 mL). To the resulting solution were added tert-butyl 4-(aminomethyl)piperidine-1-carboxylate (3.72 g, 17.4 mmol, prepared according to Carceller, Elena et al., J. Med. Chem., 1996, 39, 487), N,N-diisopropylethylamine (2.25 g, 17.4 mmol) at room temperature, and the mixture was stirred at room temperature for 18 h. Then, the mixture was quenched with saturated sodium hydrogencarbonate aqueous solution (100 mL), and extracted with dichloromethane (100 mL×4). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (v/v=1/1) to give 5.27 g (99%) of the title compound as a white solid.

1. customThe solvent and excess amounts of oxalyl chloride were removed in vacuo
2. dissolutionThe residue was dissolved in dichloromethane (80 mL)
3. customThen, the mixture was quenched with saturated sodium hydrogencarbonate aqueous solution (100 mL)
4. extractionextracted with dichloromethane (100 mL×4)
5. dry with materialThe combined organic layers were dried over magnesium sulfate
6. concentrationconcentrated in vacuo
7. customThe residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (v/v=1/1)

ORD-Eintrag

ord-b012c4b0c2564f0291860d050ddad05b

Quelldatensatz

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08362038B2