2,2-diethoxyethanethioamide

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,2-bis(ethyloxy)ethanethioamide (648 mg) (available from Maybridge International) in ethanol (30 ml) was added ethyl bromopyruvate (0.598 ml) in ethanol (1 ml). Powdered molecular sieves (200 mg) were added and the mixture heated at 90° C. for 18 h. The mixture was filtered, washed with ethanol (10 ml) and the solvent removed in vacuo. The residue was triturated with DCM (15 ml) and the solid removed by filtration and washed with DCM (10 ml). The filtrate was concentrated in vacuo. Purification by chromatography on silica gel (70 g cartridge; FlashMaster II) eluting with 0-50% ethyl acetate in cyclohexane over 40 min gave the title compound (455 mg) as a yellow oil. Powdered molecular sieves (200 mg) were added The mixture was filtered washed with ethanol (10 ml) the solvent removed in vacuo The residue was triturated with DCM (15 ml) the solid removed by filtration washed with DCM (10 ml) The filtrate was concentrated in vacuo Purification by chromatography on silica gel (70 g cartridge; FlashMaster II) eluting with 0-50% ethyl acetate in cyclohexane over 40 min

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,2-bis(ethyloxy)ethanethioamide (648 mg) (available from Maybridge International) in ethanol (30 ml) was added ethyl bromopyruvate (0.598 ml) in ethanol (1 ml). Powdered molecular sieves (200 mg) were added and the mixture heated at 90° C. for 18 h. The mixture was filtered, washed with ethanol (10 ml) and the solvent removed in vacuo. The residue was triturated with DCM (15 ml) and the solid removed by filtration and washed with DCM (10 ml). The filtrate was concentrated in vacuo. Purification by chromatography on silica gel (70 g cartridge; FlashMaster II) eluting with 0-50% ethyl acetate in cyclohexane over 40 min gave the title compound (455 mg) as a yellow oil. Powdered molecular sieves (200 mg) were added The mixture was filtered washed with ethanol (10 ml) the solvent removed in vacuo The residue was triturated with DCM (15 ml) the solid removed by filtration washed with DCM (10 ml) The filtrate was concentrated in vacuo Purification by chromatography on silica gel (70 g cartridge; FlashMaster II) eluting with 0-50% ethyl acetate in cyclohexane over 40 min

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

Procedure: 5 g (23.04 mmol) of 2-bromo-1-(4-fluorophenyl)-ethanone und 3.76 g (23.04 mmol) of 2,2-diethoxythioacetamide were stirred in 100 ml of ethanol at room temperature for 2 h. After concentrating, the residue was heated with ethyl acetate, the insolubles were filtered off, and the filtrate was evaporated. The obtained acetal (6.2 g) was stirred with 50 ml of acetone, 50 ml of water and 1 ml of 2N hydrochloric acid at room temperature for 4 h. Evaporation of the mixture yielded 4.22 g (88%) of the title compound. After concentrating the residue was heated with ethyl acetate the insolubles were filtered off the filtrate was evaporated Evaporation of the mixture

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

Procedure: A solution of diethoxythioacetamide (6.65 g; 0.04077 mol) and 2-bromo-1-(3-methylisoxazol-5-yl)ethanone (10 g; 0.04077 mol), prepared as described in the above step, in absolute ethanol (31.3 ml) was kept overnight at room temperature and then refluxed for 30 minutes. refluxed for 30 minutes

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

Procedure: 2,2-Diethoxyethanethioamide (0.654 g, 6.03 mmol; see step (iii) above) and ethylbromopyruvate (Aldrich) (1.28 g, 6.10 mmol) were dissolved in ethanol (10 mL) in the presence of 4 Å molecular sieves (1 g). The mixture was refluxed for 45 min and the solvent removed under reduced pressure. The residue was then dissolved in ethyl acetate (20 mL) and extracted with saturated. NaHCO3 solution (2×20 mL), and brine (2×20 mL). The organic fraction was then dried (MgSO4), filtered and the solvent removed under reduced pressure to yield the sub-title compound (1.452 g, 93%). The mixture was refluxed for 45 min the solvent removed under reduced pressure The residue was then dissolved in ethyl acetate (20 mL) extracted with saturated The organic fraction was then dried (MgSO4) filtered the solvent removed under reduced pressure

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

Procedure: 2,2-Diethoxyethanethioamide (0.654 g, 6.03 mmol; see step (iii) above) and ethylbromopyruvate (Aldrich) (1.28 g, 6.10 mmol) were dissolved in ethanol (10 mL) in the presence of 4 Å molecular sieves (1 g). The mixture was refluxed for 45 min and the solvent removed under reduced pressure. The residue was then dissolved in ethyl acetate (20 mL) and extracted with saturated. NaHCO3 solution (2×20 mL), and brine (2×20 mL). The organic fraction was then dried (MgSO4), filtered and the solvent removed under reduced pressure to yield the sub-title compound (1.452 g, 93%). The mixture was refluxed for 45 min the solvent removed under reduced pressure The residue was then dissolved in ethyl acetate (20 mL) extracted with saturated The organic fraction was then dried (MgSO4) filtered the solvent removed under reduced pressure

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,2-bis(ethyloxy)ethanethioamide (648 mg) (available from Maybridge International) in ethanol (30 ml) was added ethyl bromopyruvate (0.598 ml) in ethanol (1 ml). Powdered molecular sieves (200 mg) were added and the mixture heated at 90° C. for 18 h. The mixture was filtered, washed with ethanol (10 ml) and the solvent removed in vacuo. The residue was triturated with DCM (15 ml) and the solid removed by filtration and washed with DCM (10 ml). The filtrate was concentrated in vacuo. Purification by chromatography on silica gel (70 g cartridge; FlashMaster II) eluting with 0-50% ethyl acetate in cyclohexane over 40 min gave the title compound (455 mg) as a yellow oil. Powdered molecular sieves (200 mg) were added The mixture was filtered washed with ethanol (10 ml) the solvent removed in vacuo The residue was triturated with DCM (15 ml) the solid removed by filtration washed with DCM (10 ml) The filtrate was concentrated in vacuo Purification by chromatography on silica gel (70 g cartridge; FlashMaster II) eluting with 0-50% ethyl acetate in cyclohexane over 40 min

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

Procedure: 5 g (23.04 mmol) of 2-bromo-1-(4-fluorophenyl)-ethanone und 3.76 g (23.04 mmol) of 2,2-diethoxythioacetamide were stirred in 100 ml of ethanol at room temperature for 2 h. After concentrating, the residue was heated with ethyl acetate, the insolubles were filtered off, and the filtrate was evaporated. The obtained acetal (6.2 g) was stirred with 50 ml of acetone, 50 ml of water and 1 ml of 2N hydrochloric acid at room temperature for 4 h. Evaporation of the mixture yielded 4.22 g (88%) of the title compound. After concentrating the residue was heated with ethyl acetate the insolubles were filtered off the filtrate was evaporated Evaporation of the mixture

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

Procedure: A mixture of 2,2-diethoxyethanethioamide (2 g), ethyl bromopyruvate (1.61 ml), MS-4A (2 g) and EtOH (15 ml) was heated under reflux for 1 h. The mixture was concentrated, and the residue was diluted with AcOEt. The mixture was washed with water and brine successively, dried with MgSO4 and concentrated in vacuo. The residue was purified by NH silica gel column chromatography (hexane/EtOAc) to give the title compound (2.5 g) as an off-white solid. was heated under reflux for 1 h The mixture was concentrated the residue was diluted with AcOEt The mixture was washed with water and brine successively dried with MgSO4 concentrated in vacuo The residue was purified by NH silica gel column chromatography (hexane/EtOAc)

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

Procedure: A mixture of 2,2-diethoxyethanethioamide (2 g), ethyl bromopyruvate (1.61 ml), MS-4A (2 g) and EtOH (15 ml) was heated under reflux for 1 h. The mixture was concentrated, and the residue was diluted with AcOEt. The mixture was washed with water and brine successively, dried with MgSO4 and concentrated in vacuo. The residue was purified by NH silica gel column chromatography (hexane/EtOAc) to give the title compound (2.5 g) as an off-white solid. was heated under reflux for 1 h The mixture was concentrated the residue was diluted with AcOEt The mixture was washed with water and brine successively dried with MgSO4 concentrated in vacuo The residue was purified by NH silica gel column chromatography (hexane/EtOAc)

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

Procedure: 5 g (23.04 mmol) of 4-fluorophenacyl bromide and 3.76 g (23.04 mmol) of 2,2-diethoxythioacetamide in 100 ml of ethanol were stirred at room temperature for 2 h. After concentration, the residue was treated with ethyl acetate and filtered. The filtrate was concentrated and the obtained residue, which consisted of the diethyl acetal of 4-(4-fluoro-phenyl)-thiazole-2-carbaldehyde, was treated with 100 ml of acetone/water and 1 ml of 2 N hydrochloric acid. After stirring at room temperature for 2 h, the reaction mixture was evaporated. Yield: 4.22 g. After concentration the residue was treated with ethyl acetate filtered The filtrate was concentrated was treated with 100 ml of acetone/water and 1 ml of 2 N hydrochloric acid the reaction mixture was evaporated

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

Procedure: To a suspension of phosphorus pentasulfide (27 g) in dry THF (100 ml) at 0° C. under vigorous stirring, Na2CO3 (13 g) was added. The reaction mixture was stirred for 30 min at 0° C. and for 30 min at r.t., then diethoxyacetamide (6 g) was added and stirring was continued at r.t. for 70 h. The reaction was then diluted with EA, washed with 10% Na3PO4, brine, dried over Na2SO4 and the solvent removed in vacuo. The crude residue was purified by flash-chromatography (EE/PE 1/1) to give the title compound as a white solid (4.4 g). was added stirring was continued at r.t. for 70 h washed with 10% Na3PO4, brine dried over Na2SO4 the solvent removed in vacuo The crude residue was purified by flash-chromatography (EE/PE 1/1)