2-iodo-1,3-dimethoxybenzene

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: The process comprising treating 2-bromo-1,3-dimethoxybenzene, 2-iodo-1,3-dimethoxybenzene or 1,3-dimethoxybenzene with an organolithium reagent in a first solvent at a temperature of about −5° C. to about 15° C., preferably about 0° C. to about 5° C., after complete addition of the organolithium reagent, the temperature is allowed to warm to ambient temperature and the reaction mixture is stirred for about 1 to 4 hours, preferably about 2 hours, recooling the reaction mixture to about 0° C. and then adding ZnCl2 while maintaining the temperature between −5° C. and 15° C., preferably about −5° C. to about 5° C., after complete addition of ZnCl2 allowing the temperature to warm to ambient temperature and allowing the reaction mixture to stir for about 1 to 4 hours, preferably about 2 hours, recooling the reaction mixture to about 0° C. and adding methyl 2-bromo-5-nitrobenzoate, methyl 2-iodo-5-nitrobenzoate or methyl 5-nitro-2-{[(trifluoromethyl)sulfonyl]oxy}benzoate followed by addition of first transition metal catalyst and maintaining the reaction temperature between about 10° C. and about 55° C., preferably between about 20° C. and about 45° C., about 30 minutes after complete addition of first transition metal catalyst adding isopropylacetate and stirring for about 20 to about 90 minutes and then filtering to provide methyl 2′,6′-dimethoxy-4-nitro-1,1′-biphenyl-2-carboxylate; to about 0° C. to warm to ambient temperature to stir for about 1 to 4 hours, preferably about 2 hours to about 0° C. maintaining the reaction temperature between about 10° C. and about 55° C., preferably between about 20° C. and about 45° C., about 30 minutes stirring for about 20 to about 90 minutes filtering

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A cooled (−78° C.) solution of 2-iodo-1,3-dimethoxybenzene (4.119 g; 15.13 mmol) in anh. THF (40 ml) was treated dropwise with a solution of 1.6 M n-BuLi in hexanes (10.40 ml; 16.64 mmol), and the resulting mixture was stirred at −78° C., under nitrogen, for 10 min. A solution of ethyl 2-((tert-butylsulfinyl)imino)acetate (3.106 g; 15.13 mmol) in anh. THF (20 ml) was added dropwise, and stirring at −78° C. was then continued for 25 min. The reaction mixture was treated with aq. sat. NH4Cl (30 ml), water (40 ml), and Et2O (60 ml). The separated aq. layer was extracted with Et2O (2×50 ml), and the mixed organic layers were washed with brine (40 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=20/1) afforded ethyl 2-(2,6-dimethoxyphenyl)-2-(1,1-dimethylethylsulfinamido)acetate as a yellow oil. LC-MS (conditions D): tR=0.91 min.; [M+H]+: 344.45 g/mol. stirring at −78° C. was then continued for 25 min The separated aq. layer was extracted with Et2O (2×50 ml) the mixed organic layers were washed with brine (40 ml) dried over anh. MgSO4 filtered concentrated to dryness under reduced pressure Purification by FC (DCM/MeOH=20/1)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A cooled (−78° C.) solution of 2-iodo-1,3-dimethoxybenzene (4.119 g; 15.13 mmol) in anh. THF (40 ml) was treated dropwise with a solution of 1.6 M n-BuLi in hexanes (10.40 ml; 16.64 mmol), and the resulting mixture was stirred at −78° C., under nitrogen, for 10 min. A solution of ethyl 2-((tert-butylsulfinyl)imino)acetate (3.106 g; 15.13 mmol) in anh. THF (20 ml) was added dropwise, and stirring at −78° C. was then continued for 25 min. The reaction mixture was treated with aq. sat. NH4Cl (30 ml), water (40 ml), and Et2O (60 ml). The separated aq. layer was extracted with Et2O (2×50 ml), and the mixed organic layers were washed with brine (40 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=20/1) afforded ethyl 2-(2,6-dimethoxyphenyl)-2-(1,1-dimethylethylsulfinamido)acetate as a yellow oil. LC-MS (conditions D): tR=0.91 min.; [M+H]+: 344.45 g/mol. stirring at −78° C. was then continued for 25 min The separated aq. layer was extracted with Et2O (2×50 ml) the mixed organic layers were washed with brine (40 ml) dried over anh. MgSO4 filtered concentrated to dryness under reduced pressure Purification by FC (DCM/MeOH=20/1)

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A cooled (−10° C.) solution of commercially available 2-iodo-1,3-dimethoxybenzene (2.000 g; 7.57 mmol) in anh. THF (30 ml) was treated dropwise with a solution of 2 M isopropylmagnesium chloride in THF (5.10 ml; 10.20 mmol), and the mixture was further stirred at −10° C., under nitrogen, for 15 min. This mixture was then added dropwise to a cooled (−40° C.) solution of commercially available 4,4-dimethyldihydro-2H-pyran-2,6(3H)-dione (1.184 g; 8.33 mmol) and CuI (360 mg; 1.89 mmol) in anh. THF (20 ml). Stirring was continued at −40° C. for 20 min., and 2 M aq. HCl (11.5 ml) was then added dropwise. Et2O (100 ml), and aq. sat. NH4Cl (30 ml) were added, and the separated organic layer was dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Anh. DMF (20 ml), and Cs2CO3 (3.080 g; 9.45 mmol) were successively added, and stirring at rt was continued for 15 min. After cooling to 0° C., iodomethane (1.610 g; 11.34 mmol) was added dropwise, and the resulting mixture was further stirred at 0° C. for 10 min., and then at rt for 1.5 h. AcOEt (100 ml) and water (100 ml) were added, and the separated organic layer was further washed with brine (25 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=20/1) afforded methyl 5-(2,6-dimethoxyphenyl)-3,3-dimethyl-5-oxopentanoate as a yellow oil. LC-MS (conditions D): tR=1.01 min.; [M+H]+: 295.39 g/mol. This mixture was then added dropwise to Stirring was continued at −40° C. for 20 min. the separated organic layer was dried over anh. MgSO4 filtered concentrated to dryness under reduced pressure stirring at rt was continued for 15 min After cooling to 0° C. the resulting mixture was further stirred at 0° C. for 10 min. at rt for 1.5 h the separated organic layer was further washed with brine (25 ml) dried over anh. MgSO4 filtered concentrated to dryness under reduced pressure Purification by FC (DCM/MeOH=20/1)

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A cooled (−10° C.) solution of commercially available 2-iodo-1,3-dimethoxybenzene (2.000 g; 7.57 mmol) in anh. THF (30 ml) was treated dropwise with a solution of 2 M isopropylmagnesium chloride in THF (5.10 ml; 10.20 mmol), and the mixture was further stirred at −10° C., under nitrogen, for 15 min. This mixture was then added dropwise to a cooled (−40° C.) solution of commercially available 4-methyldihydro-2H-pyran-2,6(3H)-dione (970 mg; 7.57 mmol) and CuI (360 mg; 1.89 mmol) in anh. THF (20 ml). Stirring was continued at −40° C. for 20 min., and 2 M aq. HCl (11.5 ml) was then added dropwise. Et2O (100 ml), and aq. sat. NH4Cl (30 ml) were added, and the separated organic layer was dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Anh. DMF (20 ml), and Cs2CO3 (3.165 g; 9.71 mmol) were successively added, and stirring at rt was continued for 15 min. After cooling to 0° C., iodomethane (1.655 g; 11.66 mmol) was added dropwise, and the resulting mixture was further stirred at 0° C. for 10 min., and then at rt for 1.5 h. AcOEt (100 ml) and water (100 ml) were added, and the separated organic layer was further washed with brine (25 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=20/1) afforded methyl 5-(2,6-dimethoxyphenyl)-3-methyl-5-oxopentanoate as a yellow oil. LC-MS (conditions D): tR=0.97 min.; [M+H]+: 281.29 g/mol. This mixture was then added dropwise to Stirring was continued at −40° C. for 20 min. the separated organic layer was dried over anh. MgSO4 filtered concentrated to dryness under reduced pressure stirring at rt was continued for 15 min After cooling to 0° C. the resulting mixture was further stirred at 0° C. for 10 min. at rt for 1.5 h the separated organic layer was further washed with brine (25 ml) dried over anh. MgSO4 filtered concentrated to dryness under reduced pressure Purification by FC (DCM/MeOH=20/1)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A cooled (−78° C.) yellow solution of 2-iodo-1,3-dimethoxybenzene (8.553 g; 32.39 mmol) in anh. THF (175 ml), under nitrogen, was treated dropwise with a solution of 1.6 M n-BuLi in hexanes (20.25 ml; 32.40 mmol). The resulting slightly yellow solution was further stirred at −78° C. for 15 min. A yellow solution of ethyl 4-((tert-butylsulfinyl)imino)-2-methylbutanoate (6.410 g; 25.91 mmol) in anh. THF (15 ml) was then added dropwise to the cooled reaction mixture, and stirring at −78° C. was continued for 30 min. The resulting yellow reaction mixture was treated successively with aq. sat. NH4Cl (80 ml), Et2O (250 ml) and water (75 ml). The separated yellow organic layer was then washed with brine (75 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=25/1) afforded ethyl 4-(2,6-dimethoxyphenyl)-4-(1,1-dimethylethylsulfinamido)-2-methylbutanoate as an orange oil. LC-MS (conditions B): tR=0.88 min. and [M+H]+: 386.15 g/mol; tR=0.89 min. and [M+H]+: 386.14 g/mol (mixture of diastereoisomers). stirring at −78° C. was continued for 30 min The separated yellow organic layer was then washed with brine (75 ml) dried over anh. MgSO4 filtered concentrated to dryness under reduced pressure Purification by FC (DCM/MeOH=25/1)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A cooled (−78° C.) yellow solution of 2-iodo-1,3-dimethoxybenzene (8.553 g; 32.39 mmol) in anh. THF (175 ml), under nitrogen, was treated dropwise with a solution of 1.6 M n-BuLi in hexanes (20.25 ml; 32.40 mmol). The resulting slightly yellow solution was further stirred at −78° C. for 15 min. A yellow solution of ethyl 4-((tert-butylsulfinyl)imino)-2-methylbutanoate (6.410 g; 25.91 mmol) in anh. THF (15 ml) was then added dropwise to the cooled reaction mixture, and stirring at −78° C. was continued for 30 min. The resulting yellow reaction mixture was treated successively with aq. sat. NH4Cl (80 ml), Et2O (250 ml) and water (75 ml). The separated yellow organic layer was then washed with brine (75 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=25/1) afforded ethyl 4-(2,6-dimethoxyphenyl)-4-(1,1-dimethylethylsulfinamido)-2-methylbutanoate as an orange oil. LC-MS (conditions B): tR=0.88 min. and [M+H]+: 386.15 g/mol; tR=0.89 min. and [M+H]+: 386.14 g/mol (mixture of diastereoisomers). stirring at −78° C. was continued for 30 min The separated yellow organic layer was then washed with brine (75 ml) dried over anh. MgSO4 filtered concentrated to dryness under reduced pressure Purification by FC (DCM/MeOH=25/1)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A cooled (−78° C.) yellow solution of 2-iodo-1,3-dimethoxybenzene (13.798 g; 52.25 mmol) in anh. THF (200 ml), under nitrogen, was treated dropwise with a solution of 1.6 M n-BuLi in hexanes (32.66 ml; 52.25 mmol). The resulting slightly yellow solution was further stirred at −78° C. for 15 min. A yellow solution of methyl 4-((tert-butylsulfinyl)imino)butanoate (7.640 g; 34.83 mmol) in anh. THF (50 ml) was then added dropwise to the cooled reaction mixture, and stirring at −78° C. was continued for 45 min. The resulting yellow reaction mixture was treated successively with aq. sat. NH4Cl (20 ml), Et2O (250 ml) and water (75 ml). The separated yellow organic layer was then washed with brine (75 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=30/1) afforded methyl 4-(2,6-dimethoxyphenyl)-4-(1,1-dimethylethylsulfinamido)butanoate as a yellow oil. LC-MS (conditions A): tR=0.73 min.; [M+H]+: 358.34 g/mol. stirring at −78° C. was continued for 45 min The separated yellow organic layer was then washed with brine (75 ml) dried over anh. MgSO4 filtered concentrated to dryness under reduced pressure Purification by FC (DCM/MeOH=30/1)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A cooled (−78° C.) yellow solution of 2-iodo-1,3-dimethoxybenzene (13.798 g; 52.25 mmol) in anh. THF (200 ml), under nitrogen, was treated dropwise with a solution of 1.6 M n-BuLi in hexanes (32.66 ml; 52.25 mmol). The resulting slightly yellow solution was further stirred at −78° C. for 15 min. A yellow solution of methyl 4-((tert-butylsulfinyl)imino)butanoate (7.640 g; 34.83 mmol) in anh. THF (50 ml) was then added dropwise to the cooled reaction mixture, and stirring at −78° C. was continued for 45 min. The resulting yellow reaction mixture was treated successively with aq. sat. NH4Cl (20 ml), Et2O (250 ml) and water (75 ml). The separated yellow organic layer was then washed with brine (75 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=30/1) afforded methyl 4-(2,6-dimethoxyphenyl)-4-(1,1-dimethylethylsulfinamido)butanoate as a yellow oil. LC-MS (conditions A): tR=0.73 min.; [M+H]+: 358.34 g/mol. stirring at −78° C. was continued for 45 min The separated yellow organic layer was then washed with brine (75 ml) dried over anh. MgSO4 filtered concentrated to dryness under reduced pressure Purification by FC (DCM/MeOH=30/1)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A cooled (−78° C.) yellow solution of 2-iodo-1,3-dimethoxybenzene (6.337 g; 24.00 mmol) in anh. THF (130 ml), under nitrogen, was treated dropwise with a solution of 1.6 M n-BuLi in hexanes (15.0 ml; 24.00 mmol). The resulting yellow solution was further stirred at −78° C. for 15 min. A yellow solution of ethyl 6-((tert-butylsulfinyl)imino)hexanoate (5.018 g; 19.20 mmol) in anh. THF (12 ml) was then added dropwise to the cooled reaction mixture, and stirring at −78° C. was continued for 50 min. The resulting orange reaction mixture was treated successively with aq. sat. NH4Cl (65 ml), Et2O (200 ml) and water (60 ml). The separated yellow organic layer was then washed with brine (60 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=25/1) afforded ethyl 6-(2,6-dimethoxyphenyl)-6-(1,1-dimethylethylsulfinamido)hexanoate as a yellow oil. LC-MS (conditions B): tR=0.91 min.; [M+H]+: 400.05 g/mol. stirring at −78° C. was continued for 50 min The separated yellow organic layer was then washed with brine (60 ml) dried over anh. MgSO4 filtered concentrated to dryness under reduced pressure Purification by FC (DCM/MeOH=25/1)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A cooled (−78° C.) yellow solution of commercially available 2-iodo-1,3-dimethoxybenzene (9.930 g; 37.60 mmol) in anh. THF (170 ml), under nitrogen, was treated dropwise with a solution of 1.6 M n-BuLi in hexanes (23.5 ml; 37.60 mmol). The resulting slightly yellow solution was further stirred at −78° C. for 15 min. A yellow solution of methyl 5-((tert-butylsulfinyl)imino)pentanoate (5.850 g; 25.07 mmol) in anh. THF (12 ml) was then added dropwise to the cooled reaction mixture, and stirring at −78° C. was continued for 45 min. The resulting yellow reaction mixture was treated successively with aq. sat. NH4Cl (80 ml), Et2O (250 ml) and water (75 ml). The separated yellow organic layer was then washed with brine (75 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=25/1) afforded methyl 5-(2,6-dimethoxyphenyl)-5-(1,1-dimethylethylsulfinamido)pentanoate as a yellow oil. LC-MS (conditions B): tR=0.85 min.; [M+H]+: 372.34 g/mol. stirring at −78° C. was continued for 45 min The separated yellow organic layer was then washed with brine (75 ml) dried over anh. MgSO4 filtered concentrated to dryness under reduced pressure Purification by FC (DCM/MeOH=25/1)