N-methoxy-N-methyl-3-phenylpropanamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Following a procedure of Trost (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)); n-Butyllithium (2.5 M in hexanes, 10.4 ml, 26 mmol, 1.7 eq.) was added dropwise to a solution of triisopropylsilyl acetylene (5.8 ml, 26 mmol, 1.7 eq.) in THF (53 ml) at −78° C. After addition, the mixture was allowed to warm slowly to 0° C. and stirred for 1 h. The mixture was cooled to −78° C. and a solution of 83 (3.0 g, 15.3 mmol, 1 eq.) in THF (20 ml) was added dropwise. The mixture was then allowed to slowly warm to −10° C. and stirred for 1 h before being quenched by the addition of saturated aq. NH4Cl (50 ml). The mixture was extracted with EtOAc (3×30 ml) and the combined organic phases were washed with brine (50 ml) before being dried (MgSO4), filtered and concentrated to give the crude product. This was purified by column chromatography on silica, eluting with petrol/Et2O (100:0 to 98:2), giving the title product 84 as a clear, colourless oil (4.61 g, 96%). After addition The mixture was cooled to −78° C. to slowly warm to −10° C. stirred for 1 h before being quenched by the addition of saturated aq. NH4Cl (50 ml) The mixture was extracted with EtOAc (3×30 ml) the combined organic phases were washed with brine (50 ml) before being dried (MgSO4) filtered concentrated to give the crude product This was purified by column chromatography on silica eluting with petrol/Et2O (100:0 to 98:2)

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

Procedure: Following a procedure of Trost (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)); to a slurry of N,O-dimethylhydroxylamine hydrochloride (4.91 g, 50.4 mmol, 2.1 eq.) in toluene (50 ml) at −10° C. was added AlMe3 (2 M in hexanes, 25.2 ml, 50.4 mmol, 2.1 eq.) dropwise. After addition, the mixture was allowed to warm to r.t. and stirred for 1 h. The mixture was cooled to −5° C. and a solution of methyl 3-phenylpropanoate 82 (3.94 g, 24.0 mmol, 1 eq.) in toluene (40 ml) was added dropwise. The reaction mixture was then allowed to warm slowly to r.t. and stirred for 3 h. The solution was cooled to 0° C. and quenched carefully by dropwise addition of HCl and the reaction mixture was extracted with EtOAc (4×70 ml). The combined organic phases were washed with brine (50 ml) before being dried (MgSO4), filtered and concentrated to give the crude product. This was purified by column chromatography on silica, eluting with petrol/EtOAc (80:20 to 75:25), giving the Weinreb amide 83 as a clear, colourless oil (4.45 g, 97%). Analytical data consistent with the literature (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006); Murphy, J. A. et al., Org. Lett. 7, 1427-1429 (2005)). After addition The mixture was cooled to −5° C. to warm slowly to r.t. stirred for 3 h The solution was cooled to 0° C. quenched carefully by dropwise addition of HCl the reaction mixture was extracted with EtOAc (4×70 ml) The combined organic phases were washed with brine (50 ml) before being dried (MgSO4) filtered concentrated to give the crude product This was purified by column chromatography on silica eluting with petrol/EtOAc (80:20 to 75:25)

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

Procedure: Following a procedure of Trost (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)); to a slurry of N,O-dimethylhydroxylamine hydrochloride (4.91 g, 50.4 mmol, 2.1 eq.) in toluene (50 ml) at −10° C. was added AlMe3 (2 M in hexanes, 25.2 ml, 50.4 mmol, 2.1 eq.) dropwise. After addition, the mixture was allowed to warm to r.t. and stirred for 1 h. The mixture was cooled to −5° C. and a solution of methyl 3-phenylpropanoate 82 (3.94 g, 24.0 mmol, 1 eq.) in toluene (40 ml) was added dropwise. The reaction mixture was then allowed to warm slowly to r.t. and stirred for 3 h. The solution was cooled to 0° C. and quenched carefully by dropwise addition of HCl and the reaction mixture was extracted with EtOAc (4×70 ml). The combined organic phases were washed with brine (50 ml) before being dried (MgSO4), filtered and concentrated to give the crude product. This was purified by column chromatography on silica, eluting with petrol/EtOAc (80:20 to 75:25), giving the Weinreb amide 83 as a clear, colourless oil (4.45 g, 97%). Analytical data consistent with the literature (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006); Murphy, J. A. et al., Org. Lett. 7, 1427-1429 (2005)). After addition The mixture was cooled to −5° C. to warm slowly to r.t. stirred for 3 h The solution was cooled to 0° C. quenched carefully by dropwise addition of HCl the reaction mixture was extracted with EtOAc (4×70 ml) The combined organic phases were washed with brine (50 ml) before being dried (MgSO4) filtered concentrated to give the crude product This was purified by column chromatography on silica eluting with petrol/EtOAc (80:20 to 75:25)

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

Procedure: A suspension of 10.2 grams (68.1 mmol) of hydrocinnamic acid, 14.4 grams (74.9 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, 7.31 grams (74.9 mmol) of N,O-dimethylhydroxylamine hydrochloride in 250 mL of methylene chloride was cooled to 0° C. and treated with 19.1 mL (13.9 grams, 136 mmol) of triethylamine. The mixture was stirred for 16 hours with slow warming to rt and was then concentrated. The residue was taken up in 250 mL of ethyl acetate, washed with aqueous 1N hydrochloric acid solution (2×150 mL), saturated aqueous sodium hydrogencarbonate solution (2×100 mL), brine (1×100 mL), dried (Na2SO4), and evaporated to give 13.11 grams (99%) of the title compound as an oil. Anal. Calcd for C11H15NO2: C, 68.37; H, 7.82; N, 7.25. Found: C, 68.65; H, 8.11; N, 7.18. with slow warming to rt was then concentrated washed with aqueous 1N hydrochloric acid solution (2×150 mL), saturated aqueous sodium hydrogencarbonate solution (2×100 mL), brine (1×100 mL) dried (Na2SO4) evaporated

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

Procedure: To a solution of N,N,N′,N′-tetramethylethylenediamine (4.31 mL) in cyclohexane (50 ml) were added n-butyl lithium (2.46 mol/L n-hexane solution 12.2 mL) and 3-methoxythiophenol (2 g) successively under ice-cooling. The reaction mixture was stirred at room temperature overnight. To the reaction mixture was added N-methoxy-N-methyl-3-phenylpropionamide (2.76 g) under ice-cooling, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with diethyl ether. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=10/1-5/1) to give the title compound (1.2 g). cooling cooling the mixture was stirred at room temperature overnight the resulting mixture was extracted with diethyl ether The extract was washed with water dried over anhydrous magnesium sulfate The solvent was removed under reduced pressure the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=10/1-5/1)

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

Procedure: To a mixture of N,O-dimethylhydroxylamine hydrochloride (1.1 g) and pyridine (1.82 mL) in dichloromethane (50 mL) was added 3-phenylpropionyl chloride (1.52 mL) under ice-cooling, and the mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added 1 mol/L hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give the title compound (1.89 g). cooling The reaction mixture was concentrated under reduced pressure To the residue was added 1 mol/L hydrochloric acid the mixture was extracted with ethyl acetate The extract was washed with water dried over anhydrous magnesium sulfate The solvent was removed under reduced pressure

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

Procedure: To a solution of N,N,N′,N′-tetramethylethylenediamine (4.31 mL) in cyclohexane (50 ml) were added n-butyl lithium (2.46 mol/L n-hexane solution 12.2 mL) and 3-methoxythiophenol (2 g) successively under ice-cooling. The reaction mixture was stirred at room temperature overnight. To the reaction mixture was added N-methoxy-N-methyl-3-phenylpropionamide (2.76 g) under ice-cooling, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with diethyl ether. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=10/1-5/1) to give the title compound (1.2 g). cooling cooling the mixture was stirred at room temperature overnight the resulting mixture was extracted with diethyl ether The extract was washed with water dried over anhydrous magnesium sulfate The solvent was removed under reduced pressure the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=10/1-5/1)

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

Procedure: To a mixture of N,O-dimethylhydroxylamine hydrochloride (1.1 g) and pyridine (1.82 mL) in dichloromethane (50 mL) was added 3-phenylpropionyl chloride (1.52 mL) under ice-cooling, and the mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added 1 mol/L hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give the title compound (1.89 g). cooling The reaction mixture was concentrated under reduced pressure To the residue was added 1 mol/L hydrochloric acid the mixture was extracted with ethyl acetate The extract was washed with water dried over anhydrous magnesium sulfate The solvent was removed under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir: