3-[tert-butyl(dimethyl)silyl]oxy-4-methoxyaniline

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: A mixture of 3-iodophthalic acid dimethyl ester (1.0 g, 3.1 mmol), 3-(tert-butyldimethylsilanyloxy)-4-methoxyphenylamine (0.79 g, 3.1 mmol), Pd2(dba)3 (0.13 g, 0.14 mmol), rac-BINAP (0.058 g, 0.093 mmol), and cesium carbonate (1.4 g, 4.3 mmol), in 6 mL toluene was heated to reflux under nitrogen for 24 hours. The reaction mixture was cooled, diluted with CH2Cl2 (10 mL), and filtered through Celite, and the filter was washed with additional CH2Cl2 (30 mL). The filtrate was evaporated, and the residue was chromatographed using a hexanes-ethyl acetate gradient, eluting 1.0 g of the product at 90:10 hexanes-ethyl acetate, in 71% yield: 1H NMR (CDCl3) δ 0.16 (s, 6H), 0.98 (s, 9H), 3.81 (s, 3H), 3.87 (s, 3H), 3.88 (s, 3H), 6.69-6.75 (m, 2H), 6.82 (d, J=8.2 Hz, 1H), 6.95 (dd, J=7.3 Hz, J=1.1 Hz, 1H), 7.12 (dd, J=7.0 Hz, J=1.1 Hz, 1H), 7.24 (t, J=7.8 Hz, 1H), 8.04 (s, 1H). to reflux under nitrogen for 24 hours The reaction mixture was cooled filtered through Celite the filter was washed with additional CH2Cl2 (30 mL) The filtrate was evaporated the residue was chromatographed eluting 1.0 g of the product at 90:10 hexanes-ethyl acetate

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

Procedure: A mixture of tert-butyl-(2-methoxy-5-nitrophenoxy)dimethylsilane (3.0 g, 10.6 mmol) and 5% Pd—C (0.3 g) in 30 mL of ethyl acetate was hydrogenated under 50 psi of hydrogen gas for 14 hours. The mixture was filtered through Celite and the filtrate was evaporated. The residue was chromatographed using a hexanes-ethyl acetate gradient, eluting 2.0 g of the product at 85:15 hexanes-ethyl acetate, in 74% yield: 1H NMR (CDCl3) δ 0.15 (s, 6H), 0.99 (s, 9H), 3.37 (br, 2H), 3.72 (s, 3H), 6.23-6.29 (m, 2H), 6.68 (d, J=8.1 Hz, 1H). The mixture was filtered through Celite the filtrate was evaporated The residue was chromatographed eluting 2.0 g of the product at 85:15 hexanes-ethyl acetate

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

Procedure: A mixture of tert-butyl-(2-methoxy-5-nitrophenoxy)dimethylsilane (3.0 g, 10.6 mmol) and 5% Pd—C (0.3 g) in 30 mL of ethyl acetate was hydrogenated under 50 psi of hydrogen gas for 14 hours. The mixture was filtered through Celite and the filtrate was evaporated. The residue was chromatographed using a hexanes-ethyl acetate gradient, eluting 2.0 g of the product at 85:15 hexanes-ethyl acetate, in 74% yield: 1H NMR (CDCl3) δ 0.15 (s, 6H), 0.99 (s, 9H), 3.37 (br, 2H), 3.72 (s, 3H), 6.23-6.29 (m, 2H), 6.68 (d, J=8.1 Hz, 1H). The mixture was filtered through Celite the filtrate was evaporated The residue was chromatographed eluting 2.0 g of the product at 85:15 hexanes-ethyl acetate

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: A mixture of 3-iodophthalic acid dimethyl ester (1.0 g, 3.1 mmol), 3-(tert-butyldimethylsilanyloxy)-4-methoxyphenylamine (0.79 g, 3.1 mmol), Pd2(dba)3 (0.13 g, 0.14 mmol), rac-BINAP (0.058 g, 0.093 mmol), and cesium carbonate (1.4 g, 4.3 mmol), in 6 mL toluene was heated to reflux under nitrogen for 24 hours. The reaction mixture was cooled, diluted with CH2Cl2 (10 mL), and filtered through Celite, and the filter was washed with additional CH2Cl2 (30 mL). The filtrate was evaporated, and the residue was chromatographed using a hexanes-ethyl acetate gradient, eluting 1.0 g of the product at 90:10 hexanes-ethyl acetate, in 71% yield: 1H NMR (CDCl3) δ 0.16 (s, 6H), 0.98 (s, 9H), 3.81 (s, 3H), 3.87 (s, 3H), 3.88 (s, 3H), 6.69-6.75 (m, 2H), 6.82 (d, J=8.2 Hz, 1H), 6.95 (dd, J=7.3 Hz, J=1.1 Hz, 1H), 7.12 (dd, J=7.0 Hz, J=1.1 Hz, 1H), 7.24 (t, J=7.8 Hz, 1H), 8.04 (s, 1H). to reflux under nitrogen for 24 hours The reaction mixture was cooled filtered through Celite the filter was washed with additional CH2Cl2 (30 mL) The filtrate was evaporated the residue was chromatographed eluting 1.0 g of the product at 90:10 hexanes-ethyl acetate

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

Procedure: A mixture of tert-butyl-(2-methoxy-5-nitrophenoxy)dimethylsilane (3.0 g, 10.6 mmol) and 5% Pd—C (0.3 g) in 30 mL of ethyl acetate was hydrogenated under 50 psi of hydrogen gas for 14 hours. The mixture was filtered through Celite and the filtrate was evaporated. The residue was chromatographed using a hexanes-ethyl acetate gradient, eluting 2.0 g of the product at 85:15 hexanes-ethyl acetate, in 74% yield: 1H NMR (CDCl3) δ 0.15 (s, 6H), 0.99 (s, 9H), 3.37 (br, 2H), 3.72 (s, 3H), 6.23-6.29 (m, 2H), 6.68 (d, J=8.1 Hz, 1H). The mixture was filtered through Celite the filtrate was evaporated The residue was chromatographed eluting 2.0 g of the product at 85:15 hexanes-ethyl acetate