1-bromo-3-fluoro-2-iodobenzene

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

Procedure: Prepared from 2,4-dimethyl-benzenethiol and 1-bromo-3-fluoro-2-iodo-benzene.

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

Procedure: Prepared from 4-methoxy-benzenethiol and 1-bromo-3-fluoro-2-iodo-benzene (prepared from 2-bromo-6-fluoro-phenylamine by diazotization according to the general procedure by Tunney and Stille J. Org. Chem. 1987, 52, 748-753).

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

Procedure: Prepared from 2,4-dimethyl-benzenethiol and 1-bromo-3-fluoro-2-iodo-benzene.

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

Procedure: Prepared from 4-methoxy-benzenethiol and 1-bromo-3-fluoro-2-iodo-benzene (prepared from 2-bromo-6-fluoro-phenylamine by diazotization according to the general procedure by Tunney and Stille J. Org. Chem. 1987, 52, 748-753).

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

Procedure: Pd(Ph3P)4 in a 500-mL round-bottom flask under N2 atmosphere was treated sequentially with a solution of 1-bromo-3-fluoro-2-iodo-benzene (30 g, 0.1 mol) in toluene (250 mL), a solution of 2N aq Na2CO3 (200 mL) and 3-methyl phenylboronic acid in ethanol (62 mL). This mixture was heated at reflux under N2 for 12 h, then cooled to rt. The mixture was partitioned between water and EtOAc, the combined organic layers were washed with brine, dried over MgSO4, evaporated and purified by column chromatography to give 6-bromo-2-fluoro-3′-methyl-biphenyl (12 g). 1H NMR (400 MHz, CD3OD): 7.03 (m, 2H), 7.48-7.04 (m, 4H), 7.50 (d, 1H). This mixture was heated at reflux under N2 for 12 h The mixture was partitioned between water and EtOAc the combined organic layers were washed with brine dried over MgSO4 evaporated purified by column chromatography

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

Procedure: Pd(Ph3P)4 in a 500-mL round-bottom flask under N2 atmosphere was treated sequentially with a solution of 1-bromo-3-fluoro-2-iodo-benzene (30 g, 0.1 mol) in toluene (250 mL), a solution of 2N aq Na2CO3 (200 mL) and 3-methyl phenylboronic acid in ethanol (62 mL). This mixture was heated at reflux under N2 for 12 h, then cooled to rt. The mixture was partitioned between water and EtOAc, the combined organic layers were washed with brine, dried over MgSO4, evaporated and purified by column chromatography to give 6-bromo-2-fluoro-3′-methyl-biphenyl (12 g). 1H NMR (400 MHz, CD3OD): 7.03 (m, 2H), 7.48-7.04 (m, 4H), 7.50 (d, 1H). This mixture was heated at reflux under N2 for 12 h The mixture was partitioned between water and EtOAc the combined organic layers were washed with brine dried over MgSO4 evaporated purified by column chromatography

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

Procedure: Pd(Ph3P)4 in a 500-mL round-bottom flask under N2 atmosphere was treated sequentially with a solution of 1-bromo-3-fluoro-2-iodo-benzene (30 g, 0.1 mol) in toluene (250 mL), a solution of 2N aq Na2CO3 (200 mL) and 3-methyl phenylboronic acid in ethanol (62 mL). This mixture was heated at reflux under N2 for 12 h, then cooled to rt. The mixture was partitioned between water and EtOAc, the combined organic layers were washed with brine, dried over MgSO4, evaporated and purified by column chromatography to give 6-bromo-2-fluoro-3′-methyl-biphenyl (12 g). 1H NMR (400 MHz, CD3OD): 7.03 (m, 2H), 7.48-7.04 (m, 4H), 7.50 (d, 1H). This mixture was heated at reflux under N2 for 12 h The mixture was partitioned between water and EtOAc the combined organic layers were washed with brine dried over MgSO4 evaporated purified by column chromatography

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of diisopropylamine (76 mL, 0.4 mol) in dry THF (664 mL) and n-hexane (220 mL) was added 2.5 M/L n-BuLi (160 mL. 0.4 mol) dropwise at −78° C. during a period of 1 h. The mixture was stirred for 1 h at −78° C. Then a solution of 1-bromo-3-fluoro-benzene (69 g, 0.4 mol) in dry THF (300 mL) at −78° C. was added to the above mixture dropwise. After stirring for an additional 1 h at −78° C., the mixture was added a solution of iodine (101 g, 0.4 mol) in dry THF (400 mL) dropwise at −78° C. The temperature was raised from −78° C. to rt during 2 h. After stirring for 18 h at rt, the mixture was concentrated in vacuo to give crude product (120 g) which was distilled under reduced pressure to afford 1-bromo-3-fluoro-2-iodo-benzene (110 g). 1H NMR (400 MHz, DMSO): 7.24-7.19 (t, 1H), 7.38-7.32 (m, 1H), 7.55-7.53 (d, 1H). After stirring for an additional 1 h at −78° C. The temperature was raised from −78° C. to rt during 2 h After stirring for 18 h at rt the mixture was concentrated in vacuo to give crude product (120 g) which was distilled under reduced pressure

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

Procedure: Pd(Ph3P)4 in a 500-mL round-bottom flask under N2 atmosphere was treated sequentially with a solution of 1-bromo-3-fluoro-2-iodo-benzene (30 g, 0.1 mol) in toluene (250 mL), a solution of 2N aq Na2CO3 (200 mL) and 3-methyl phenylboronic acid in ethanol (62 mL). This mixture was heated at reflux under N2 for 12 h, then cooled to rt. The mixture was partitioned between water and EtOAc. The combined organic layers were washed with brine, dried over MgSO4, evaporated and purified by column chromatography to give 6-bromo-2-fluoro-3′-methyl-biphenyl (12 g). 1H NMR (400 MHz, CD3OD): 7.03 (m, 2H), 7.48-7.04 (m, 4H), 7.50 (d, 1H). This mixture was heated at reflux under N2 for 12 h The mixture was partitioned between water and EtOAc The combined organic layers were washed with brine dried over MgSO4 evaporated purified by column chromatography

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

Procedure: Pd(Ph3P)4 in a 500-mL round-bottom flask under N2 atmosphere was treated sequentially with a solution of 1-bromo-3-fluoro-2-iodo-benzene (30 g, 0.1 mol) in toluene (250 mL), a solution of 2N aq Na2CO3 (200 mL) and 3-methyl phenylboronic acid in ethanol (62 mL). This mixture was heated at reflux under N2 for 12 h, then cooled to rt. The mixture was partitioned between water and EtOAc. The combined organic layers were washed with brine, dried over MgSO4, evaporated and purified by column chromatography to give 6-bromo-2-fluoro-3′-methyl-biphenyl (12 g). 1H NMR (400 MHz, CD3OD): 7.03 (m, 2H), 7.48-7.04 (m, 4H), 7.50 (d, 1H). This mixture was heated at reflux under N2 for 12 h The mixture was partitioned between water and EtOAc The combined organic layers were washed with brine dried over MgSO4 evaporated purified by column chromatography

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of diisopropylamine (76 mL, 0.4 mol) in dry THF (664 mL) and n-hexane (220 mL) was added 2.5 M n-BuLi (160 mL. 0.4 mol) dropwise at −78° C. during a period of 1 h. The mixture was stirred for 1 h at −78° C. Then a solution of 1-bromo-3-fluoro-benzene (69 g, 0.4 mol) in dry THF (300 mL) at −78° C. was added to the above mixture dropwise. After stirring for an additional 1 h at −78° C., the mixture was added a solution of iodine (101 g, 0.4 mol) in dry THF (400 mL) dropwise at −78° C. The temperature was raised from −78° C. to rt during 2 h. After stirring for 18 h at rt, the mixture was concentrated in vacuo to give crude product (120 g) which was distilled under reduced pressure to afford 1-bromo-3-fluoro-2-iodobenzene (110 g). 1H NMR (400 MHz, DMSO): 7.24-7.19 (t, 1H), 7.38-7.32 (m, 1H), 7.55-7.53 (d, 1H). After stirring for an additional 1 h at −78° C. The temperature was raised from −78° C. to rt during 2 h After stirring for 18 h at rt the mixture was concentrated in vacuo to give crude product (120 g) which was distilled under reduced pressure

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of diisopropylamine (76 mL, 0.4 mol) in dry THF (664 mL) and n-hexane (220 mL) was added 2.5 M n-BuLi (160 mL. 0.4 mol) dropwise at −78° C. during a period of 1 h. The mixture was stirred for 1 h at −78° C. Then a solution of 1-bromo-3-fluoro-benzene (69 g, 0.4 mol) in dry THF (300 mL) at −78° C. was added to the above mixture dropwise. After stirring for an additional 1 h at −78° C., the mixture was added a solution of iodine (101 g, 0.4 mol) in dry THF (400 mL) dropwise at −78° C. The temperature was raised from −78° C. to rt during 2 h. After stirring for 18 h at rt, the mixture was concentrated in vacuo to give crude product (120 g) which was distilled under reduced pressure to afford 1-bromo-3-fluoro-2-iodobenzene (110 g). 1H NMR (400 MHz, DMSO): 7.24-7.19 (t, 1H), 7.38-7.32 (m, 1H), 7.55-7.53 (d, 1H). After stirring for an additional 1 h at −78° C. The temperature was raised from −78° C. to rt during 2 h After stirring for 18 h at rt the mixture was concentrated in vacuo to give crude product (120 g) which was distilled under reduced pressure