4-chloro-2,2-dimethyl-1,3-benzoxazine

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

Procedure: To a solution of 2,2-dimethyl-2H-benzo[e][1,3]oxazin-4(3H)-one (100 g, 0.56 mol) in POCl3 (500 mL) was added PCl5 (170 g, 0.84 mol) at the room temperature. The mixture was hearted at 60° C. overnight. The solvent was removed by distillation under atmospheric pressure and the residue was distilled under reduced pressure (85-86° C., 2.5 mmHg) to give 4-chloro-2,2-dimethyl-2H-benzo[e][1,3]oxazine (50 g, 45%). 1H NMR (400 MHz, CDCl3) δ 7.55 (dd, J=1.6, 8.4 Hz, 1H), 7.38 (dt, J=1.6, 8.0 Hz 1H), 6.95 (t, J=6.8 Hz 1H), 6.79 (d, J=8.0 Hz 1H), 1.61 (s, 6H). The solvent was removed by distillation under atmospheric pressure the residue was distilled under reduced pressure (85-86° C., 2.5 mmHg)

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

Procedure: To a solution of 2,2-dimethyl-2H-benzo[e][1,3]oxazin-4(3H)-one (100 g, 0.56 mol) in POCl3 (500 mL) was added PCl5 (170 g, 0.84 mol) at the room temperature. The mixture was hearted at 60° C. overnight. The solvent was removed by distillation under atmospheric pressure and the residue was distilled under reduced pressure (85-86° C., 2.5 mmHg) to give 4-chloro-2,2-dimethyl-2H-benzo[e][1,3]oxazine (50 g, 45%). 1H NMR (400 MHz, CDCl3) δ 7.55 (dd, J=1.6, 8.4 Hz, 1H), 7.38 (dt, J=1.6, 8.0 Hz 1H), 6.95 (t, J=6.8 Hz 1H), 6.79 (d, J=8.0 Hz 1H), 1.61 (s, 6H). The solvent was removed by distillation under atmospheric pressure the residue was distilled under reduced pressure (85-86° C., 2.5 mmHg)

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

Procedure: A solution of 172 mg (0.87 mmol) of 4-chloro-2,2-dimethyl-(2H)-1,3-benzoxazine (K. Wachi and A. Terada, Chem. Pharm. Bull, 1980, 28, 465-472) and 215 mg (1.75 mmol) of 3-ethylpyridine N-oxide (S. Hibino and E. Sugino, J. Heterocycl Chem., 1990, 27, 175) in 1.6 mL of methylene chloride was heated to reflux for 9 h with stirring. After cooling the reaction, 30 mL ethyl acetate was added and the mixture was washed in succession with 10 mL saturated sodium bicarbonate and 10 mL of saturated aqueous sodium chloride. The organic solution was dried (sodium sulfate), decanted, and evaporated to give a yellow liquid. Flash column chromatography on 17 g of silica gel, eluting with 100 mL of 5% ethyl acetate/hexane and 500 mL of 7% ethyl acetate/hexane furnished 84 mg (33% yield) of 3-(5-ethyl-2-pyridinyl)-2,2-dimethyl-2,3-dihydro-(4H)-1,3-benzoxazin-4-one as a colorless syrup. to reflux for 9 h After cooling was added the mixture was washed in succession with 10 mL saturated sodium bicarbonate and 10 mL of saturated aqueous sodium chloride The organic solution was dried (sodium sulfate) decanted evaporated to give a yellow liquid Flash column chromatography on 17 g of silica gel, eluting with 100 mL of 5% ethyl acetate/hexane and 500 mL of 7% ethyl acetate/hexane

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

Procedure: To a solution of 2,2-dimethyl-2H-benzo[e][1,3]oxazin-4(3H)-one (100 g, 0.56 mol) in POCl3 (500 mL) was added PCl5 (170 g, 0.84 mol) at the room temperature. The mixture was hearted at 60° C. overnight. The solvent was removed by distillation under atmospheric pressure and the residue was distilled under reduced pressure (85-86° C., 2.5 mmHg) to give 4-chloro-2,2-dimethyl-2H-benzo[e][1,3]oxazine (50 g, 45%). 1H NMR (400 MHz, CDCl3) δ 7.55 (dd, J=1.6, 8.4 Hz, 1H), 7.38 (dt, J=1.6, 8.0 Hz 1H), 6.95 (t, J=6.8 Hz 1H), 6.79 (d, J=8.0 Hz 1H), 1.61 (s, 6H). The solvent was removed by distillation under atmospheric pressure the residue was distilled under reduced pressure (85-86° C., 2.5 mmHg)