METHYL 5-(BENZYLOXYCARBONYL)-2,4-DIMETHYL-3-PYRROLEPROPIONATE

67-56-1

99602-66-1

20303-31-5

d) Preparation of methyl 5-(benzyloxycarbonyl)-2,4-dimethyl-3-pyrrolepropionate (Compound 3): to a 2.5 liter Keller round bottom flask equipped with a reflux condenser, a thermometer, a dropping funnel, and an argon conduit under argon protection, a methanol solution (710 mL) of sodium (2.8 g) was added. A solution of tetrahydrofuran (THF, 430 mL) of compound 4 (111.00 g, 0.28 mol) was slowly added dropwise over 10 minutes at room temperature. After the dropwise addition, stirring of the reaction mixture was continued for 1 hour. The progress of the reaction was monitored by HPLC and after confirming that the reaction was complete, the reaction was quenched by the addition of acetic acid (7 mL). Subsequently, the volatile components were evaporated under reduced pressure. The resulting crude product was dissolved in ethanol (490 mL) and diluted by adding water (280 mL). The mixture was stirred at 0 °C for 1 h to induce precipitation of the product and the precipitate was subsequently collected by filtration. The precipitate was washed with a mixture of ethanol/water (250 mL/250 mL) and dried under reduced pressure to give the final compound 3 in white solid form (53.31 g, 60% yield). The product was characterized by 1H NMR (300 MHz, CDCl3): δ 2.25 (s, 3H, CH3), 2.31 (s, 3H, CH3), 2.45 (t, 2H, CH2), 2.71 (t, 2H, CH2), 3.67 (s, 3H, CH3), 5.30 (s, 2H, CH2), 7.40 (m, 5H, Ar-H ), 8.60 (broad single peak, 1H, NH).RP-HPLC analytical conditions: HP Hypersil BDS-C18 column (125 × 4 mm, 25°C), mobile phase acetonitrile (ACN)-water gradient elution containing 0.1% trifluoroacetic acid (TFA) (1 to 100% ACN for 10 min, followed by a 2-min hold at 100% ACN). Flow rate 1 mL/min, detection wavelength 220 nm. Sample preparation: 1 mg of sample was dissolved in 1.5 mL of acetonitrile. Retention time (Rt): 8.53 min (purity >98%).