3-ethoxy-4-propan-2-yloxybenzaldehyde

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Ethoxy-4-isopropoxybenzaldehyde (WO 2004072101) (24 g, 115 mmol) was dissolved in a 7N MeOH solution of ammonia (200 mL) and the whole was cooled to 0° C. Trimethylsilyl cyanide (24 mL, 180 mmol) was added and the reaction mixture was stirred overnight with gradual warming to rt. The reaction product was concentrated to provide 2-amino-2-(3-ethoxy-4-isopropoxyphenyl)acetonitrile (29 g, 100%) as a yellow oil. The oil (23 g) was dissolved in ethyl ether (460 mL), cooled to 0° C., and HCl (g) was bubbled through the solution for 5 min. The resulting precipitate was filtered and dried on the high vac to provide Intermediate 13A (19 g, 72%) as a yellow solid. with gradual warming to rt The reaction product was concentrated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Ethoxy-4-isopropoxybenzaldehyde (WO 2004072101) (24 g, 115 mmol) was dissolved in a 7N MeOH solution of ammonia (200 mL) and the whole was cooled to 0° C. Trimethylsilyl cyanide (24 mL, 180 mmol) was added and the reaction mixture was stirred overnight with gradual warming to rt. The reaction product was concentrated to provide 2-amino-2-(3-ethoxy-4-isopropoxyphenyl)acetonitrile (29 g, 100%) as a yellow oil. The oil (23 g) was dissolved in ethyl ether (460 mL), cooled to 0° C., and HCl (g) was bubbled through the solution for 5 min. The resulting precipitate was filtered and dried on the high vac to provide Intermediate 13A (19 g, 72%) as a yellow solid. with gradual warming to rt The reaction product was concentrated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Ethoxy-4-isopropoxybenzaldehyde (WO 2004072101) (24 g, 115 mmol) was dissolved in a 7N MeOH solution of ammonia (200 mL) and the whole was cooled to 0° C. Trimethylsilyl cyanide (24 mL, 180 mmol) was added and the reaction mixture was stirred overnight with gradual warming to rt. The reaction product was concentrated to provide 2-amino-2-(3-ethoxy-4-isopropoxyphenyl)acetonitrile (29 g, 100%) as a yellow oil. The oil (23 g) was dissolved in ethyl ether (460 mL), cooled to 0° C., and HCl (g) was bubbled through the solution for 5 min. The resulting precipitate was filtered and dried on the high vac to provide Intermediate 13A (19 g, 72%) as a yellow solid. with gradual warming to rt The reaction product was concentrated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Ethoxy-4-isopropoxybenzaldehyde (WO 2004072101) (24 g, 115 mmol) was dissolved in a 7N MeOH solution of ammonia (200 mL) and the whole was cooled to 0° C. Trimethylsilyl cyanide (24 mL, 180 mmol) was added and the reaction mixture was stirred overnight with gradual warming to rt. The reaction product was concentrated to provide 2-amino-2-(3-ethoxy-4-isopropoxyphenyl)acetonitrile (29 g, 100%) as a yellow oil. The oil (23 g) was dissolved in ethyl ether (460 mL), cooled to 0° C., and HCl (g) was bubbled through the solution for 5 min. The resulting precipitate was filtered and dried on the high vac to provide Intermediate 13A (19 g, 72%) as a yellow solid. with gradual warming to rt The reaction product was concentrated

反応条件: temp:0.00; pressure:0.00; stir:

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: A mixture of 3-ethoxy-4-isopropoxybenzaldehyde (1.78 g, 8.55 mmol), 4-aminobenzonitrile (1.01 g, 8.55 mmol), and 5 g 4 A molecular sieves in 20 mL toluene was refluxed with azeotropic removal of water for 2 h. The mixture was filtered and concentrated to afford 2.29 g of Intermediate 1.1 as a pale yellow solid. The mixture was filtered concentrated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 141A (7.42 g, 35:6 mmol) and 4-cyanoaniline (4.21 g, 35.6 mmol) in methanol (120 mL) was stirred at 60° C. for 2 h. The reaction was cooled to 0° C. and p-toluenesulfonylmethyl isocyanide (6.95 g, 35.6 mmol) was added followed by dropwise addition of boron trifluoride etherate (13.5 mL, 107 mmol). After stirring for 30 min at 0° C., the reaction was allowed to warm to rt and stirring was continued for 2 h. Water (4 mL) was added and bright yellow precipitate was observed after stirring for 2 days. The solvent was removed and the residue was redissolved in ethyl acetate. The precipitate was filtered and dried to give 7.89 g of 141B as a white solid. 1H NMR (400 MHz, Methanol-d4) δ ppm 1.18-1.20 (m, 6H) 1.28 (t, J=6.98, 3H) 3.62 (s, 3H) 3.90-3.98 (m, 2H) 4.40-4.50 (m, 1H) 5.06 (s, 1H) 6.59 (d, J=8.90 Hz, 2H) 6.80-7.00 (m, 3H) 7.29 (d, J=8.90 Hz, 2H). to warm to rt stirring was continued for 2 h after stirring for 2 days The solvent was removed the residue was redissolved in ethyl acetate The precipitate was filtered dried

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 3-ethoxy-4-hydroxybenzaldehyde (20.0 g, 120 mmol) in dimethylformamide (250 mL) was added potassium carbonate (33.1 g, 240 mmol) then 2-iodopropane (18 mL, 180 mmol). The reaction mixture was heated to 45° C. and stirred for 3 h. After cooling to rt, the crude reaction mixture was extracted with ethyl acetate (3×). The combined extracts were then washed with water (3×) then brine and dried over sodium sulfate. The solvent was removed to give 24 g of 141A as a yellow oil. LC-MS: 231.17 (M+Na)+. After cooling to rt the crude reaction mixture was extracted with ethyl acetate (3×) The combined extracts were then washed with water (3×) brine and dried over sodium sulfate The solvent was removed

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Ethoxy-4-isopropoxybenzaldehyde (WO 2004072101) (24 g, 115 mmol) was dissolved in a 7N MeOH solution of ammonia (200 mL) and the whole was cooled to 0° C. Trimethylsilyl cyanide (24 mL, 180 mmol) was added and the reaction mixture was stirred overnight with gradual warming to rt. The reaction product was concentrated to provide 2-amino-2-(3-ethoxy-4-isopropoxyphenyl)acetonitrile (29 g, 100%) as a yellow oil. The oil (23 g) was dissolved in ethyl ether (460 mL), cooled to 0° C., and HCl (g) was bubbled through the solution for 5 min. The resulting precipitate was filtered and dried on the high vac to provide Intermediate 13A (19 g, 72%) as a yellow solid. with gradual warming to rt The reaction product was concentrated