(2-aminophenyl)boronic acid

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: The general procedure described in Example 3 was used with 3-chlorobenzoic acid (157 mg, 1.00 mmol), 2-aminophenylboronic acid (205 mg, 1.50 mmol), Pd(OAc)2 (2.2 mg, 0.010 mmol, 1 mol %), sodium 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl-3′-sulfonate (10.0 mg, 0.020 mmol, 2 mol %), K2CO3 (414 mg, 3.00 mmol), water (2.0 mL), 12 h, 100° C. The product was isolated as a white solid (203 mg, 95%). Mp=170° C. (lit.=173-175° C.) 1H NMR (400 MHz, d4-MeOH) δ: 8.07 (m, 1H), 7.99 (d, 1H, J=7.6 Hz), 7.65 (d, 1H, J=8.0 Hz), 7.53 (t, 1H, J=7.6 Hz), 7.13 (td, 1H, J=1.6 Hz, J=7.6 Hz), 6.84 (d, 1H, J=8.0 Hz), 6.77 (t, 1H, J=7.6 Hz). 13C NMR (125 MHz, d4-MeOH) δ: 169.9, 145.1, 141.7, 134.8, 132.6, 131.4, 131.4, 130.1, 129.9, 129.5, 128.3, 120.0, 117.6.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (The following reaction is done in an oxygenfree N2 atmosphere.) Add ethanol (0.8 mL), Tetrakis-(triphenylphosphine)-palladium(0) (30 mg, 2.2 mol %) and Na2CO3 decahydrate (944 mg, 3.30 mmol; presolved in 1.2 mL H2O) subsequently to dissolved 2-Amino-benzeneboronic acid (70) (201 mg, 1.30 mmol) in toluene (6.0 mL). Degas the reaction mixture for 5 times and flood with N2 again. Add (3-Bromo-phenyl)-acetic acid methyl ester (69) (270 mg, 1.18 mmol) in toluene (6.0 mL), degas again (5 times) and stir the reaction solution overnight at 100° C. Partition the reaction solution between EtOAc and brine (1+1) and extract the separated aqueous layer 3 times with EtOAc. Wash combined organic layer with brine and dry with Na2SO4. Remove solvent under reduced pressure and purify the crude product by preparative radial chromatography (silica gel 60 PF, CyH/EtOAc 3+1) to obtain (2′-Amino-biphenyl-3-yl)-acetic acid methyl ester (71) as an orange oil (304 mg, 81%). 1H NMR (400 MHz, CDCl3): 3.66 (s, 2H); 3.69 (s, 3H); 3.62-3.86 (br.s, 2H); 6.75 (d, 1H, J=8.1 Hz); 6.80 (t, 1H, J=7.3 Hz); 7.11 (d, 1 H, J=7.3 Hz); 7.15 (d, 1H, J=8.1 Hz); 7.22-7.26 (br.m, 1H); 7.32-7.42 (m, 3H). (The following reaction Degas the reaction mixture for 5 times and flood with N2 again Partition the reaction solution between EtOAc and brine (1+1) extract the separated aqueous layer 3 times with EtOAc Wash dry with Na2SO4 Remove solvent under reduced pressure and purify the crude product by preparative radial chromatography (silica gel 60 PF, CyH/EtOAc 3+1)

Conditions: temp:0.00; pressure:0.00; stir: