N-[(2-chlorophenyl)methyl]-3-hydroxy-2,2-dimethylpropanamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-(2-chlorobenzyl)-3-hydroxy-2,2-dimethylpropanamide (0.50 g, 2.07 mmol) in THF (5 mL) were added phthalimide (0.457 g, 3.10 mmol, 1.5 equiv.) and PPh3 (0.813 g, 3.10 mmol, 1.5 equiv.). DIAD (600 μL, 3.10 mmol, 1.5 equiv.) was added dropwise into the reaction mixture. The resulting mixture was stirred overnight. LC/MS indicated that starting material was consumed. The reaction mixture was concentrated. The resulting residue was purified on silica gel column a mixture of hexanes and ethyl acetate to give N-(2-chlorobenzyl)-3-(1,3-dioxoisoindolin-2-yl)-2,2-dimethylpropanamide (0.50 g, 65%). LRMS (M+H+) m/z 371.1. was consumed The reaction mixture was concentrated The resulting residue was purified on silica gel column a mixture of hexanes and ethyl acetate

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 3-hydroxy-2,2-dimethylpropanoate (1.0 g, 7.57 mmol) and 2-chlorobenzylamine (1.09 mL, 9.08 mmol, 1.2 equiv.) in toluene (10 mL) was added trimethylaluminum (2M in hexanes, 5.6 mL, 11.4 mmol, 1.5 equiv.). The reaction mixture was stirred at 80° C. for 2 hours. The reaction mixture was concentrated. The resulting residue was dissolved in EtOAc (100 mL). The organic layer was washed with saturated NaHCO3, dried over Na2SO4, and concentrated. The resulting residue was purified on silica gel column using a mixture of hexanes and ethyl acetate to give N-(2-chlorobenzyl)-3-hydroxy-2,2-dimethylpropanamide (1.55 g, 84%). LRMS (M+H+) m/z 242.1. The reaction mixture was concentrated The resulting residue was dissolved in EtOAc (100 mL) The organic layer was washed with saturated NaHCO3 dried over Na2SO4 concentrated The resulting residue was purified on silica gel column a mixture of hexanes and ethyl acetate

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 3-hydroxy-2,2-dimethylpropanoate (1.0 g, 7.57 mmol) and 2-chlorobenzylamine (1.09 mL, 9.08 mmol, 1.2 equiv.) in toluene (10 mL) was added trimethylaluminum (2M in hexanes, 5.6 mL, 11.4 mmol, 1.5 equiv.). The reaction mixture was stirred at 80° C. for 2 hours. The reaction mixture was concentrated. The resulting residue was dissolved in EtOAc (100 mL). The organic layer was washed with saturated NaHCO3, dried over Na2SO4, and concentrated. The resulting residue was purified on silica gel column using a mixture of hexanes and ethyl acetate to give N-(2-chlorobenzyl)-3-hydroxy-2,2-dimethylpropanamide (1.55 g, 84%). LRMS (M+H+) m/z 242.1. The reaction mixture was concentrated The resulting residue was dissolved in EtOAc (100 mL) The organic layer was washed with saturated NaHCO3 dried over Na2SO4 concentrated The resulting residue was purified on silica gel column a mixture of hexanes and ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-(2-chlorobenzyl)-3-hydroxy-2,2-dimethylpropanamide (30 mg, 0.12 mmol), in CH2Cl2 were added DMAP and 4-ethylphenylisocyanate (21 μL, 0.15 mmol, 1.5 equiv.). The reaction mixture was stirred for 1 h. The reaction mixture was concentrated. The resulting residue was to purify on RP-HPLC to give 3-(2-chlorobenzylamino)-2,2-dimethyl-3-oxopropyl 4-ethylphenylcarbamate (10 mg, 17%). LRMS (M+H+) m/z 389.1. The reaction mixture was concentrated to purify on RP-HPLC

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-(2-chlorobenzyl)-3-hydroxy-2,2-dimethylpropanamide (30 mg, 0.12 mmol), in CH2Cl2 were added DMAP and 4-ethylphenylisocyanate (21 μL, 0.15 mmol, 1.5 equiv.). The reaction mixture was stirred for 1 h. The reaction mixture was concentrated. The resulting residue was to purify on RP-HPLC to give 3-(2-chlorobenzylamino)-2,2-dimethyl-3-oxopropyl 4-ethylphenylcarbamate (10 mg, 17%). LRMS (M+H+) m/z 389.1. The reaction mixture was concentrated to purify on RP-HPLC

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 3-hydroxy-2,2-dimethylpropanoate (1 g, 7.31 mmol) and 2-chlorobenzylamine (1 mL, 8.75 mmol, 1.2 equiv.) in toluene (7 mL) was added trimethylaluminum (2 M in hexane, 5.4 mL, 10.8 mmol, 1.5 equiv.). The reaction mixture was stirred at 80° C. for 2 h. The reaction mixture was quenched with saturated NaHCO3. The resulting mixture was extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated to give N-(2-chlorobenzyl)-3-hydroxy-2,2-dimethylpropanamide (1.5 g, 85%), which was used without further purification. LRMS (M+H+) m/z 242.1. The reaction mixture was quenched with saturated NaHCO3 The resulting mixture was extracted with EtOAc The organic layer was dried over Na2SO4 concentrated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-(2-chlorobenzyl)-3-hydroxy-2,2-dimethylpropanamide (0.50 g, 2.07 mmol) in THF (5 mL) were added phthalimide (0.457 g, 3.10 mmol, 1.5 equiv.) and PPh3 (0.813 g, 3.10 mmol, 1.5 equiv.). DIAD (600 μL, 3.10 mmol, 1.5 equiv.) was added dropwise into the reaction mixture. The resulting mixture was stirred overnight. LC/MS indicated that starting material was consumed. The reaction mixture was concentrated. The resulting residue was purified on silica gel column a mixture of hexanes and ethyl acetate to give N-(2-chlorobenzyl)-3-(1,3-dioxoisoindolin-2-yl)-2,2-dimethylpropanamide (0.50 g, 65%). LRMS (M+H+) m/z 371.1. was consumed The reaction mixture was concentrated The resulting residue was purified on silica gel column a mixture of hexanes and ethyl acetate

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 3-hydroxy-2,2-dimethylpropanoate (1.0 g, 7.57 mmol) and 2-chlorobenzylamine (1.09 mL, 9.08 mmol, 1.2 equiv.) in toluene (10 mL) was added trimethylaluminum (2M in hexanes, 5.6 mL, 11.4 mmol, 1.5 equiv.). The reaction mixture was stirred at 80° C. for 2 hours. The reaction mixture was concentrated. The resulting residue was dissolved in EtOAc (100 mL). The organic layer was washed with saturated NaHCO3, dried over Na2SO4, and concentrated. The resulting residue was purified on silica gel column using a mixture of hexanes and ethyl acetate to give N-(2-chlorobenzyl)-3-hydroxy-2,2-dimethylpropanamide (1.55 g, 84%). LRMS (M+H+) m/z 242.1. The reaction mixture was concentrated The resulting residue was dissolved in EtOAc (100 mL) The organic layer was washed with saturated NaHCO3 dried over Na2SO4 concentrated The resulting residue was purified on silica gel column a mixture of hexanes and ethyl acetate