1-cyclopropylpropan-2-one

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: A 25 mL round bottomed flask was charged with Ti(OEt)4 (technical grade, 0.37 mL, 1.4 mmol) and 1-cyclopropylpropan-2-one (79.0 mg, 0.81 mmol) in THF (1.45 mL), under an argon atmosphere. Then 2-methylpropane-2-sulfinamide (88.7 mg, 0.73 mmol) was added and the reaction mixture was heated to reflux overnight. After cooling to room temperature the reaction mixture was poured onto brine (1.7 mL), with rapid stirring. The resulting suspension was filtered through a pad of celite. The filtrate was concentrated under reduced pressure to afford crude 2-methyl-propane-2-sulfinic acid [2-cyclopropyl-1-methyl-eth-(E)-ylidene]-amide which was taken directly to the next step without purification. the reaction mixture was heated to reflux overnight was poured onto brine (1.7 mL), with rapid stirring The resulting suspension was filtered through a pad of celite The filtrate was concentrated under reduced pressure

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

実験手順: A 25 mL round bottomed flask was charged with Ti(OEt)4 (technical grade, 0.37 mL, 1.4 mmol) and 1-cyclopropylpropan-2-one (79.0 mg, 0.81 mmol) in THF (1.45 mL), under an argon atmosphere. Then 2-methylpropane-2-sulfinamide (88.7 mg, 0.73 mmol) was added and the reaction mixture was heated to reflux overnight. After cooling to room temperature the reaction mixture was poured onto brine (1.7 mL), with rapid stirring. The resulting suspension was filtered through a pad of celite. The filtrate was concentrated under reduced pressure to afford crude 2-methyl-propane-2-sulfinic acid [2-cyclopropyl-1-methyl-eth-(E)-ylidene]-amide which was taken directly to the next step without purification. the reaction mixture was heated to reflux overnight was poured onto brine (1.7 mL), with rapid stirring The resulting suspension was filtered through a pad of celite The filtrate was concentrated under reduced pressure

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

実験手順: To a solution of 1-cyclopropyl-propan-2-one (CAN 4160-75-2; 1.0 g, 10.2 mmol) and aqueous ammonia (25% in water, 10 mL) in ethanol (10 mL) was added ammonium chloride (1.63 g, 30.6 mmol). The reaction mixture was stirred at ambient temperature for 1 hour. To this was added potassium cyanide (1 g, 15.30 mmol) portion wise, and the reaction mixture was stirred at ambient temperature for 12 h. Ice water (50 mL) was added and extracted with ethyl acetate (3×50 mL). The organic phases were washed with ice-water, combined, dried with Na2SO4 and concentrated in vacuo to give the title compound (0.8 g, 62.99%) as yellow oil; NMR (400 MHz, DMSO) δ=2.52 (bds, 2H); 1.6-1.5 (m, 1H); 1.49-1.4 (m, 1H); 1.39 (S, 3H); 0.85-0.75 (m, 1H); 0.49-0.44 (m, 2H); 0.16-0.14 (m, 2H). the reaction mixture was stirred at ambient temperature for 12 h extracted with ethyl acetate (3×50 mL) The organic phases were washed with ice-water dried with Na2SO4 concentrated in vacuo

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

実験手順: To a solution of 1-cyclopropyl-propan-2-one (1.0 g, 10.2 mmol; CAN 4160-75-2) and aqueous ammonia (25% in water, 15 mL) in EtOH (10 mL) was added ammonium chloride (1.63 g, 30.61 mmol). The reaction mixture was stirred at ambient temperature for 1 hour. To this was added potassium cyanide (900 mg, 15.3 mmol) portion wise and the reaction mixture was stirred at ambient temperature for 12 h. Ice water (50 mL) was added and the mixture was extracted with ethyl acetate (3×50 mL). The organic phases were washed with ice water, combined, dried with Na2SO4 and concentrated in vacuo to give the title compound (0.8 g, 63%) as yellow oil. 1H-NMR (DMSO, 400 MHz): 0.14-0.16 (d, 6.4 Hz, 2H); 0.45-0.49 (d, 6.4 Hz, 2H); 0.78-0.85 (m, 1H); 1.39 (s, 3H); 1.46-1.51 (m, 1H), 1.53-1.63 (m, 1H); 2.52 (br s, 2H). the reaction mixture was stirred at ambient temperature for 12 h the mixture was extracted with ethyl acetate (3×50 mL) The organic phases were washed with ice water dried with Na2SO4 concentrated in vacuo

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

実験手順: To a solution of 1-cyclopropyl-propan-2-one (1.0 g, 10.2 mmol; CAN 4160-75-2) and aqueous ammonia (25% in water, 15 mL) in EtOH (10 mL) was added ammonium chloride (1.63 g, 30.61 mmol). The reaction mixture was stirred at ambient temperature for 1 hour. To this was added potassium cyanide (900 mg, 15.3 mmol) portion wise and the reaction mixture was stirred at ambient temperature for 12 h. Ice water (50 mL) was added and the mixture was extracted with ethyl acetate (3×50 mL). The organic phases were washed with ice water, combined, dried with Na2SO4 and concentrated in vacuo to give the title compound (0.8 g, 63%) as yellow oil. 1H-NMR (DMSO, 400 MHz): 0.14-0.16 (d, 6.4 Hz, 2H); 0.45-0.49 (d, 6.4 Hz, 2H); 0.78-0.85 (m, 1H); 1.39 (s, 3H); 1.46-1.51 (m, 1H), 1.53-1.63 (m, 1H); 2.52 (br s, 2H). the reaction mixture was stirred at ambient temperature for 12 h the mixture was extracted with ethyl acetate (3×50 mL) The organic phases were washed with ice water dried with Na2SO4 concentrated in vacuo

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

実験手順: To a solution of 1-cyclopropyl-propan-2-one (CAN 4160-75-2; 1.0 g, 10.2 mmol) and aqueous ammonia (25% in water, 10 mL) in ethanol (10 mL) was added ammonium chloride (1.63 g, 30.6 mmol). The reaction mixture was stirred at ambient temperature for 1 hour. To this was added potassium cyanide (1 g, 15.30 mmol) portion wise, and the reaction mixture was stirred at ambient temperature for 12 h. Ice water (50 mL) was added and extracted with ethyl acetate (3×50 mL). The organic phases were washed with ice-water, combined, dried with Na2SO4 and concentrated in vacuo to give the title compound (0.8 g, 62.99%) as yellow oil; NMR (400 MHz, DMSO) δ=2.52 (bds, 2H); 1.6-1.5 (m, 1H); 1.49-1.4 (m, 1H); 1.39 (S, 3H); 0.85-0.75 (m, 1H); 0.49-0.44 (m, 2H); 0.16-0.14 (m, 2H). the reaction mixture was stirred at ambient temperature for 12 h extracted with ethyl acetate (3×50 mL) The organic phases were washed with ice-water dried with Na2SO4 concentrated in vacuo

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

実験手順: To a solution of 1-cyclopropyl-propan-2-one (1.0 g, 10.2 mmol; CAN 4160-75-2) and aqueous ammonia (25% in water, 15 mL) in EtOH (10 mL) was added ammonium chloride (1.63 g, 30.61 mmol). The reaction mixture was stirred at ambient temperature for 1 hour. To this was added potassium cyanide (900 mg, 15.3 mmol) portion wise and the reaction mixture was stirred at ambient temperature for 12 h. Ice water (50 mL) was added and the mixture was extracted with ethyl acetate (3×50 mL). The organic phases were washed with ice water, combined, dried with Na2SO4 and concentrated in vacuo to give the title compound (0.8 g, 63%) as yellow oil. 1H-NMR (DMSO, 400 MHz): 0.14-0.16 (d, 6.4 Hz, 2H); 0.45-0.49 (d, 6.4 Hz, 2H); 0.78-0.85 (m, 1H); 1.39 (s, 3H); 1.46-1.51 (m, 1H), 1.53-1.63 (m, 1H); 2.52 (br s, 2H). the reaction mixture was stirred at ambient temperature for 12 h the mixture was extracted with ethyl acetate (3×50 mL) The organic phases were washed with ice water dried with Na2SO4 concentrated in vacuo

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

実験手順: To a solution of 1-cyclopropylpropan-2-one (0.2 mL, 0.08 mmol in 1:1 THF:DMSO) was added 6-(3-fluorophenyl)-N-(piperidin-4-yl)nicotinamide (in 1:1 THF:DMSO, 0.2 mL, 0.08 mmol), sodium triacetoxyborohydride dispersion (0.33 mL, 2.5 eq, in 1:1 THF:DMSO) and glacial acetic acid (0.01 mL). The reaction mixture was stirred at room temperature for 16-24 h and then aqueous K2CO3 (3 M, 0.2 mL) and ethanol (0.55 mL) was added. The reaction was shaken for 30 min and then the mixture was filtered and the filtrate concentrated and the residue purified by RP-HPLC to give the desired product. LC/MS=382.4 (M+H) observed, 382.23 expected. The reaction was shaken for 30 min the mixture was filtered the filtrate concentrated the residue purified by 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 1-cyclopropylpropan-2-one (0.2 mL, 0.08 mmol in 1:1 THF:DMSO) was added 6-(3-fluorophenyl)-N-(piperidin-4-yl)nicotinamide (in 1:1 THF:DMSO, 0.2 mL, 0.08 mmol), sodium triacetoxyborohydride dispersion (0.33 mL, 2.5 eq, in 1:1 THF:DMSO) and glacial acetic acid (0.01 mL). The reaction mixture was stirred at room temperature for 16-24 h and then aqueous K2CO3 (3 M, 0.2 mL) and ethanol (0.55 mL) was added. The reaction was shaken for 30 min and then the mixture was filtered and the filtrate concentrated and the residue purified by RP-HPLC to give the desired product. LC/MS=382.4 (M+H) observed, 382.23 expected. The reaction was shaken for 30 min the mixture was filtered the filtrate concentrated the residue purified by RP-HPLC

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

実験手順: A 25 mL round bottomed flask was charged with Ti(OEt)4 (technical grade, 0.37 mL, 1.4 mmol) and 1-cyclopropylpropan-2-one (79.0 mg, 0.81 mmol) in THF (1.45 mL), under an argon atmosphere. Then 2-methylpropane-2-sulfinamide (88.7 mg, 0.73 mmol) was added and the reaction mixture was heated to reflux overnight. After cooling to room temperature the reaction mixture was poured onto brine (1.7 mL), with rapid stirring. The resulting suspension was filtered through a pad of celite. The filtrate was concentrated under reduced pressure to afford crude 2-methyl-propane-2-sulfinic acid [2-cyclopropyl-1-methyl-eth-(E)-ylidene]-amide which was taken directly to the next step without purification. the reaction mixture was heated to reflux overnight was poured onto brine (1.7 mL), with rapid stirring The resulting suspension was filtered through a pad of celite The filtrate was concentrated under reduced pressure