methyl 4-oxobut-2-enoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (2.82 g, 0.117 mol) was dissolved in 30 ml of absolute ethanol at 0° C. Valeramidine hydrochloride (16.71 g, 0.123 mol) was added to this solution, and after 15 minutes the solution was filtered and the collected solid was washed with 20 ml of ethanol and 50 ml of benzene. The combined filtrates were diluted with 750 ml of benzene, 15 g (0.117 mol) of methyl 3-formylacrylate was added, and the mixture was refluxed for 18.5 h using a trap to remove water. The solvents were removed under vacuum and the residue slurried in ether. Evaporation of the ether solution gave the title compound as an oil. after 15 minutes the solution was filtered the collected solid was washed with 20 ml of ethanol and 50 ml of benzene was added the mixture was refluxed for 18.5 h to remove water The solvents were removed under vacuum Evaporation of the ether solution

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (2.82 g, 0,117 mol) was dissolved in 30 ml of absolute ethanol at 0° C. Valeramidine hydrochloride (16.71 g, 0.123 mol) was added to this solution, and after 15 minutes the solution was filtered and the collected solid was washed with 20 ml of ethanol and 50 ml of benzene. The combined filtrates were diluted with 750 ml of benzene, 15 g (0.117 mol) of methyl 3-formylacrylate was added, and the mixture was refluxed for 18.5 h using a trap to remove water. The solvents were removed under vacuum and the residue slurried in ether. Evaporation of the ether solution gave the title compound as an oil. after 15 minutes the solution was filtered the collected solid was washed with 20 ml of ethanol and 50 ml of benzene was added the mixture was refluxed for 18.5 h to remove water The solvents were removed under vacuum Evaporation of the ether solution

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (2.82 g, 0,117 mol) was dissolved in 30 ml of absolute ethanol at 0° C. Valeramidine hydrochloride (16.71 g, 0.123 mol) was added to this solution, and after 15 minutes the solution was filtered and the collected solid was washed with 20 ml of ethanol and 50 ml of benzene. The combined filtrates were diluted with 750 ml of benzene, 15 g (0.117 mol) of methyl 3-formylacrylate was added, and the mixture was refluxed for 18.5 h using a trap to remove water. The solvents were removed under vacuum and the residue slurried in ether. Evaporation of the ether solution gave the title compound as an oil. after 15 minutes the solution was filtered the collected solid was washed with 20 ml of ethanol and 50 ml of benzene was added the mixture was refluxed for 18.5 h to remove water The solvents were removed under vacuum Evaporation of the ether solution

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared according to the general procedure from methyl 4-oxo-butenoate (171 mg, 1.50 mmol), 1-methyl-1H-indole (64 μL, 0.50 mmol), TFA (7.7 μL, 0.10 mmol) and (2S,5S)-5-benzyl-2-tert-butyl-3-methyl-imidazolidin-4-one (24.6 mg, 0.100 mmol) in CH2Cl2 (0.90 mL) and isopropanol (0.10 mL) at −85° C. for 21 h to provide, after silica gel chromatography (5:47:47 acetone/CH2Cl2/hexanes), the title compound as a colorless oil (109 mg, 89% yield, 91% ec). IR (film) 2937, 2833, 2729, 1732, 1623, 1545, 1477, 1436, 1379, 1332, 1228, 1171, 1042, 1016, 980, 773, 742 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.81 (s, 1H, CHO), 7.67 (d, J=8.4 Hz, 1H, ArH), 7.33-7.23 (m, 2H, ArH), 7.15 (ddd, J=1.2, 7.6, 7.8 Hz, 1H, ArH), 6.98 (s, 1H, NCH), 4.44 (dd, J=5.4, 9.3 Hz, 1H, ArH), 3.76 (s, 3H, NCH3), 3.69 (s, 3H, OCH3), 3.47 (dd, J=9.3, 18.6 Hz, 1H, CH2CO); 2.94 (dd, J=5.1, 18.3 Hz, 1H, CH2CO); 13C NMR (75 MHz, CDCl3) δ 200.1, 173.8, 137.0, 126.9, 126.5, 122.1, 119.5, 119.1, 110.8, 109.6, 52.5, 46.8, 36.5, 33.0; HRMS (CI) exact mass calcd for (C14H15NO3) requires m/z 245.1048, found m/z 153.1151. [α]D=−123.6 (c=1.0, CHCl3). The enantiomeric ratio was determined by HPLC analysis of the alcohol, obtained by NaBH4 reduction of the aldehyde, using a Chiracel AS and AS guard column (3:97 isopropanol/hexanes, 1 mL/min); S isomer tr=71.7 min and R isomer tr=76.3 min. Prepared to provide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This example describes a Friedel-Crafts alkylation reaction of 1-phenyl-pyrrolidine and 4-oxo-butenoic acid methyl ester, catalyzed by the hydrochloride salt of (1), to provide (R)-4-oxo-2-(4-pyrrolidin-1-yl-phenyl)-butyric acid methyl ester.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (2.82 g, 0.117 mol) was dissolved in 30 ml of absolute ethanol at 0° C. Valeramidine hydrochloride (16.71 g, 0.123 mol) was added to this solution, and after 15 minutes the solution was filtered and the collected solid was washed with 20 ml of ethanol and 50 ml of benzene. The combined filtrates were diluted with 750 ml of benzene, 15 g (0.117 mol) of methyl 3-formylacrylate was added, and the mixture was refluxed for 18.5 h using a trap to remove water. The solvents were removed under vacuum and the residue slurried in ether. Evaporation of the ether solution gave the title compound as an oil. after 15 minutes the solution was filtered the collected solid was washed with 20 ml of ethanol and 50 ml of benzene was added the mixture was refluxed for 18.5 h to remove water The solvents were removed under vacuum Evaporation of the ether solution

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (2.82 g, 0,117 mol) was dissolved in 30 ml of absolute ethanol at 0° C. Valeramidine hydrochloride (16.71 g, 0.123 mol) was added to this solution, and after 15 minutes the solution was filtered and the collected solid was washed with 20 ml of ethanol and 50 ml of benzene. The combined filtrates were diluted with 750 ml of benzene, 15 g (0.117 mol) of methyl 3-formylacrylate was added, and the mixture was refluxed for 18.5 h using a trap to remove water. The solvents were removed under vacuum and the residue slurried in ether. Evaporation of the ether solution gave the title compound as an oil. after 15 minutes the solution was filtered the collected solid was washed with 20 ml of ethanol and 50 ml of benzene was added the mixture was refluxed for 18.5 h to remove water The solvents were removed under vacuum Evaporation of the ether solution