1-(3-chlorophenyl)propan-2-one

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

実験手順: A mixture of cesium carbonate (9.80 g, 30.1 mmol) and methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (9.90 g, 30.1 mmol) in DMF (75 mL) was stirred at 23° C. for 45 min before 1-(3-chlorophenyl)propan-2-one (6.09 g, 36.1 mmol) and additional cesium carbonate (9.80 g, 30.1 mmol) were added. The resulting mixture was stirred for 2.5 h. The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C. The concentrated mixture was partitioned between water (100 mL) and ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to give the title compound as a 1:1 racemic mixture of cis and trans diastereomers, which was used without further purification. MS: m/z=392.1 (M+Na). were added The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C The concentrated mixture was partitioned between water (100 mL) and ethyl acetate (2×200 mL) The combined organic layers were washed with brine dried over sodium sulfate concentrated

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

実験手順: A mixture of cesium carbonate (9.80 g, 30.1 mmol) and methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (9.90 g, 30.1 mmol) in DMF (75 mL) was stirred at 23° C. for 45 min before 1-(3-chlorophenyl)propan-2-one (6.09 g, 36.1 mmol) and additional cesium carbonate (9.80 g, 30.1 mmol) were added. The resulting mixture was stirred for 2.5 h. The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C. The concentrated mixture was partitioned between water (500 mL) and ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to give the title compound as a 1:1 racemic mixture of diastereomers, which was used without further purification. MS: m/z=314.1 (M−t-Bu+1). were added The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C The concentrated mixture was partitioned between water (500 mL) and ethyl acetate (2×200 mL) The combined organic layers were washed with brine dried over sodium sulfate concentrated

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

実験手順: A mixture of cesium carbonate (9.80 g, 30.1 mmol) and methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (9.90 g, 30.1 mmol) in DMF (75 mL) was stirred at 23° C. for 45 min before 1-(3-chlorophenyl)propan-2-one (6.09 g, 36.1 mmol) and additional cesium carbonate (9.80 g, 30.1 mmol) were added. The resulting mixture was stirred for 2.5 h. The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C. The concentrated mixture was partitioned between water (500 mL) and ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to give the title compound as a 1:1 racemic mixture of diastereomers, which was used without further purification. MS: m/z=314.1 (M−t-Bu+1). were added The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C The concentrated mixture was partitioned between water (500 mL) and ethyl acetate (2×200 mL) The combined organic layers were washed with brine dried over sodium sulfate concentrated

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

実験手順: A mixture of cesium carbonate (9.80 g, 30.1 mmol) and methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (9.90 g, 30.1 mmol) in DMF (75 mL) was stirred at ambient temperature for 45 min before 1-(3-chlorophenyl)propan-2-one (6.09 g, 36.1 mmol) and additional cesium carbonate (9.80 g, 30.1 mmol) were added. The resulting mixture was stirred for 2.5 h. The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C. The concentrated mixture was partitioned between water (500 mL) and ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo to give the title compound as a 1:1 racemic mixture of diastereomers, which was used without further purification. MS: m/z=314.1 (M−t-Bu+1). were added The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C The concentrated mixture was partitioned between water (500 mL) and ethyl acetate (2×200 mL) The combined organic layers were washed with brine dried over sodium sulfate concentrated in vacuo

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

実験手順: A mixture of cesium carbonate (9.80 g, 30.1 mmol) and methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (9.90 g, 30.1 mmol) in DMF (75 mL) was stirred at ambient temperature for 45 min before 1-(3-chlorophenyl)propan-2-one (6.09 g, 36.1 mmol) and additional cesium carbonate (9.80 g, 30.1 mmol) were added. The resulting mixture was stirred for 2.5 h. The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C. The concentrated mixture was partitioned between water (500 mL) and ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo to give the title compound as a 1:1 racemic mixture of diastereomers, which was used without further purification. MS: m/z=314.1 (M−t-Bu+1). were added The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C The concentrated mixture was partitioned between water (500 mL) and ethyl acetate (2×200 mL) The combined organic layers were washed with brine dried over sodium sulfate concentrated in vacuo

反応条件: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 0° C., a suspension of 60% w/w NaH/mineral oil (7.13 g, 0.176 mol) in THF (250 mL) was treated dropwise with a solution of ethyl 2-(diethoxyphosphoryl)acetate (39.5 g, 0.176 mol) in THF (72 mL) over a 30 min period. The reaction was stirred for another 30 minutes, and a solution of 1-(3-chlorophenyl)propan-2-one (19.7 g, 0.117 mol) in THF (108 mL) was added dropwise over 1 h (reaction was kept at 0° C. during addition). The reaction was allowed to warm to 23° C. overnight and quenched with saturated aqueous NH4Cl (250 mL). After 2 h, the mixture was diluted with water (250 mL) and hexane (100 mL). The organic phase was collected. The aqueous layer was extracted with EtOAc (2×150 mL). Combined organic phases were dried (MgSO4), filtered, and concentrated, giving crude ethyl 4-(3-chlorophenyl)-3-methylbut-2-enoate as a mixture of E and Z isomers. The residue was carried onward without further purification. (˜25 grams). The 1H NMR reported below is from a crude mixture containing both the E and Z isomer. 1H NMR (400 MHz, CDCl3) δ 7.24-7.22 (m, 2H), 7.16 (s, 1H), 7.06-7.04 (m, 1H); 5.67 (s, 1H); 4.18-4.13 (dd, 2H); 3.40 (s, 2H), 2.11 (s, 3H), 1.30-1.26 (t, 3H). (reaction was kept at 0° C. during addition) quenched with saturated aqueous NH4Cl (250 mL) After 2 h the mixture was diluted with water (250 mL) and hexane (100 mL) The organic phase was collected The aqueous layer was extracted with EtOAc (2×150 mL) Combined organic phases were dried (MgSO4) filtered concentrated

反応条件: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 0° C., a suspension of 60% w/w NaH/mineral oil (7.13 g, 0.176 mol) in THF (250 mL) was treated dropwise with a solution of ethyl 2-(diethoxyphosphoryl)acetate (39.5 g, 0.176 mol) in THF (72 mL) over a 30 min period. The reaction was stirred for another 30 minutes, and a solution of 1-(3-chlorophenyl)propan-2-one (19.7 g, 0.117 mol) in THF (108 mL) was added dropwise over 1 h (reaction was kept at 0° C. during addition). The reaction was allowed to warm to 23° C. overnight and quenched with saturated aqueous NH4Cl (250 mL). After 2 h, the mixture was diluted with water (250 mL) and hexane (100 mL). The organic phase was collected. The aqueous layer was extracted with EtOAc (2×150 mL). Combined organic phases were dried (MgSO4), filtered, and concentrated, giving crude ethyl 4-(3-chlorophenyl)-3-methylbut-2-enoate as a mixture of E and Z isomers. The residue was carried onward without further purification. (˜25 grams). The 1H NMR reported below is from a crude mixture containing both the E and Z isomer. 1H NMR (400 MHz, CDCl3) δ 7.24-7.22 (m, 2H), 7.16 (s, 1H), 7.06-7.04 (m, 1H); 5.67 (s, 1H); 4.18-4.13 (dd, 2H); 3.40 (s, 2H), 2.11 (s, 3H), 1.30-1.26 (t, 3H). (reaction was kept at 0° C. during addition) quenched with saturated aqueous NH4Cl (250 mL) After 2 h the mixture was diluted with water (250 mL) and hexane (100 mL) The organic phase was collected The aqueous layer was extracted with EtOAc (2×150 mL) Combined organic phases were dried (MgSO4) filtered concentrated

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

実験手順: A mixture of cesium carbonate (9.80 g, 30.1 mmol) and methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (9.90 g, 30.1 mmol) in DMF (75 mL) was stirred at ambient temperature for 45 min before 1-(3-chlorophenyl)propan-2-one (6.09 g, 36.1 mmol) and additional cesium carbonate (9.80 g, 30.1 mmol) were added. The resulting mixture was stirred for 2.5 h. The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C. The concentrated mixture was partitioned between water (500 mL) and ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo to give the title compound as a 1:1 racemic mixture of diastereomers, which was used without further purification. MS: m/z=314.1 (M−t-Bu+1). were added The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C The concentrated mixture was partitioned between water (500 mL) and ethyl acetate (2×200 mL) The combined organic layers were washed with brine dried over sodium sulfate concentrated in vacuo

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

実験手順: A mixture of cesium carbonate (9.80 g, 30.1 mmol) and methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (9.90 g, 30.1 mmol) in DMF (75 mL) was stirred at 23° C. for 45 min before 1-(3-chlorophenyl)propan-2-one (6.09 g, 36.1 mmol) and additional cesium carbonate (9.80 g, 30.1 mmol) were added. The resulting mixture was stirred for 2.5 h. The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C. The concentrated mixture was partitioned between water (100 mL) and ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to give the title compound as a 1:1 racemic mixture of cis and trans diastereomers, which was used without further purification. MS: m/z=392.1 (M+Na). were added The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C The concentrated mixture was partitioned between water (100 mL) and ethyl acetate (2×200 mL) The combined organic layers were washed with brine dried over sodium sulfate concentrated

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

実験手順: A mixture of cesium carbonate (9.80 g, 30.1 mmol) and methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (9.90 g, 30.1 mmol) in DMF (75 mL) was stirred at 23° C. for 45 min before 1-(3-chlorophenyl)propan-2-one (6.09 g, 36.1 mmol) and additional cesium carbonate (9.80 g, 30.1 mmol) were added. The resulting mixture was stirred for 2.5 h. The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C. The concentrated mixture was partitioned between water (100 mL) and ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to give the title compound as a 1:1 racemic mixture of cis and trans diastereomers, which was used without further purification. MS: m/z=392.1 (M+Na). were added The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C The concentrated mixture was partitioned between water (100 mL) and ethyl acetate (2×200 mL) The combined organic layers were washed with brine dried over sodium sulfate concentrated

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

実験手順: A mixture of cesium carbonate (9.80 g, 30.1 mmol) and methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (9.90 g, 30.1 mmol) in DMF (75 mL) was stirred at 23° C. for 45 min before 1-(3-chlorophenyl)propan-2-one (6.09 g, 36.1 mmol) and additional cesium carbonate (9.80 g, 30.1 mmol) were added. The resulting mixture was stirred for 2.5 h. The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C. The concentrated mixture was partitioned between water (500 mL) and ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to give the title compound as a 1:1 racemic mixture of diastereomers, which was used without further purification. MS: m/z=314.1 (M-t-Bu+1). were added The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C The concentrated mixture was partitioned between water (500 mL) and ethyl acetate (2×200 mL) The combined organic layers were washed with brine dried over sodium sulfate concentrated

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

実験手順: A mixture of cesium carbonate (9.80 g, 30.1 mmol) and methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (9.90 g, 30.1 mmol) in DMF (75 mL) was stirred at 23° C. for 45 min before 1-(3-chlorophenyl)propan-2-one (6.09 g, 36.1 mmol) and additional cesium carbonate (9.80 g, 30.1 mmol) were added. The resulting mixture was stirred for 2.5 h. The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C. The concentrated mixture was partitioned between water (100 mL) and ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to give the title compound as a 1:1 racemic mixture of cis and trans diastereomers, which was used without further purification. MS: m/z=392.1 (M+Na). were added The majority of the DMF was then removed under reduced pressure at a bath temperature of <40° C The concentrated mixture was partitioned between water (100 mL) and ethyl acetate (2×200 mL) The combined organic layers were washed with brine dried over sodium sulfate concentrated