1-morpholin-4-ylbutane-1,3-dione

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 33 ml (0.38 mol) of morpholine were added dropwise at −5 to 0° C. to a solution of 30 g of diketene (0.36 mol) in 300 ml tetrahydrofuran. After 1 h stirring at 0° C. no more starting material was detected by thin layer chromatography. The reaction mixture was evaporated and the residue purified by column chromatography. This gave 49.48 g (0.29 mol, 81% yield) of a white solid. The reaction mixture was evaporated the residue purified by column chromatography

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

Procedure: To a solution of 1-morpholin-4-yl-butane-1,3-dione (0.53 g, 3.1 mmol) in 1,2-dichloroethane (30 mL) stirred at 0° C., N-bromosuccinimide (0.55 mg, 3.1 mmol) was added in small portions and the mixture was stirred for 1 h. The solution was washed with brine (3×5 mL), dried over MgSO4 and concentrated below 30° C. 2-Bromo-1-morpholin-4-yl-butane-1,3-dione 0.76 g, 3.04 mmol, 98.1%, LCMS/BB_LCMS01(+)/: M+1=250, 252, Rt: 1.831 min] was obtained as a yellowish oil. The solution was washed with brine (3×5 mL) dried over MgSO4 concentrated below 30° C

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

Procedure: To a solution of 1-morpholin-4-yl-butane-1,3-dione (0.53 g, 3.1 mmol) in 1,2-dichloroethane (30 mL) stirred at 0° C., N-bromosuccinimide (0.55 mg, 3.1 mmol) was added in small portions and the mixture was stirred for 1 h. The solution was washed with brine (3×5 mL), dried over MgSO4 and concentrated below 30° C. 2-Bromo-1-morpholin-4-yl-butane-1,3-dione 0.76 g, 3.04 mmol, 98.1%, LCMS/BB_LCMS01(+)/: M+1=250, 252, Rt: 1.831 min] was obtained as a yellowish oil. The solution was washed with brine (3×5 mL) dried over MgSO4 concentrated below 30° C

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

Procedure: 150 mg (0.73 mmol) N-[3-(trifluoromethyl)phenyl]urea, 96 mg (0.73 mmol) 4-cyanobenzaldehyde, 63 mg (0.37 mmol) 4-(4-morpholinyl)-4-oxo-2-butanone and 220 mg polyphosphoric acid ethyl ester are suspended in 3 ml of THF. The mixture is stirred at reflux for 18 hours. After cooling down to room temperature, the solvent is removed in vacuo and the residue is purified by column chromatography on silica with dichloromethane/methanol as eluent. at reflux for 18 hours the solvent is removed in vacuo the residue is purified by column chromatography on silica with dichloromethane/methanol as eluent

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

Procedure: 150 mg (0.73 mmol) N-[3-(trifluoromethyl)phenyl]urea, 96 mg (0.73 mmol) 4-cyanobenzaldehyde, 63 mg (0.37 mmol) 4-(4-morpholinyl)-4-oxo-2-butanone and 220 mg polyphosphoric acid ethyl ester are suspended in 3 ml of THF. The mixture is stirred at reflux for 18 hours. After cooling down to room temperature, the solvent is removed in vacuo and the residue is purified by column chromatography on silica with dichloromethane/methanol as eluent. at reflux for 18 hours the solvent is removed in vacuo the residue is purified by column chromatography on silica with dichloromethane/methanol as eluent

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 33 ml (0.38 mol) of morpholine were added dropwise at −5 to 0° C. to a solution of 30 g of diketene (0.36 mol) in 300 ml tetrahydrofuran. After 1 h stirring at 0° C. no more starting material was detected by thin layer chromatography. The reaction mixture was evaporated and the residue purified by column chromatography. This gave 49.48 g (0.29 mol, 81% yield) of a white solid. The reaction mixture was evaporated the residue purified by column chromatography

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

Procedure: To a solution of 1-morpholin-4-yl-butane-1,3-dione (0.53 g, 3.1 mmol) in 1,2-dichloroethane (30 mL) stirred at 0° C., N-bromosuccinimide (0.55 mg, 3.1 mmol) was added in small portions and the mixture was stirred for 1 h. The solution was washed with brine (3×5 mL), dried over MgSO4 and concentrated below 30° C. 2-Bromo-1-morpholin-4-yl-butane-1,3-dione 0.76 g, 3.04 mmol, 98.1%, LCMS/BB_LCMS01(+)/: M+1=250, 252, Rt: 1.831 min] was obtained as a yellowish oil. The solution was washed with brine (3×5 mL) dried over MgSO4 concentrated below 30° C