4-Methylmorpholine → tert-butyl (2R)-2-(2-methoxy-2-oxoethyl)pyrrolidine-1-carboxylate

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

(R)-1-(tert-Butyloxycarbonyl)pyrrolidin-2-yl-carboxylic acid (9.7 g, 48 mmol) is dissolved in THF (250 mL) cooled to −30° C. and treated with NMM (5.75 mL, 52 mmol), isobutyl chloroformate (6.79 mL, 52 mmol) and stirred for 20 min. The reaction mixture is filtered and the filtrate is added to a solution of diazomethane (˜71 mmol) in ether (200 mL) at 0° C. The reaction mixture is stirred for 20 min. then quenched with acetic acid dropwise. The solvent is removed under vacuo and the residue is dissolved in methanol (100 mL) and treated with a solution of silver benzoate (2.18 g, 9.5 mmol) in triethylamine (21.4 mL) for 35 min. The reaction mixture is concentrated, diluted with ethyl acetate (600 mL) and washed with saturated sodium bicarbonate (3×150 mL), water (3×150 mL), potasium sulfite (3×150 mL) and brine. The organic layer is dried (MgSO4) and concentrated; flash chromatography gives the title compound as a clear oil (5.3 g, 21.8 mmol). 1H NMR (CDCl3, 300 MHz) □ 4.1(br.s., 1H), 3.66(s, 3H), 3.38-3.28(m, 2H), 2.92-2.80(m, 1H), 2.30(dd, 1H), 2.10-1.98(m, 1H), 1.90-1.65(m, 3H), 1.43(s, 9H).

Herkunft & Nachweise