4-(2-methoxyphenyl)morpholine

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(2-methoxyphenyl)morpholine (200 mg, 1.02 mmol) in CH2Cl2 (20 mL) was added BBr3 (1 mL) at 0° C. The mixture was stirred for 2 h at 0° C. The mixture was then added drop wise to ice-water (50 mL) and the mixture treated with CH2Cl2 (2×20 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4 and concentrated to give the yellow solid which was used in next step without further purification (165 mg Yield 80%). LCMS (m/z): 180.1 (M+1). The combined organic layers were washed with brine (30 mL) dried over Na2SO4 concentrated to give the yellow solid which was used in next step without further purification (165 mg Yield 80%)

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

Procedure: To a solution of 1-iodo-2-methoxybenzene (1 g, 4.28 mmol) in dioxane (10 mL) was added morpholine (446.8 mg, 5.12 mmol), Pd2(dba)3 (100 mg, 0.1 mmol), Xantphos (200 mg, 0.3 mmol) and t-BuONa (671 mg, 6.0 mmol). Under a N2 atmosphere the reaction mixture was heated at reflux temperature for 16 h. The solvent was then removed and the residue dissolved in ethyl acetate and washed with water. The separated organic layer was concentrated to give the crude product which was used in next step without further purification (578 mg Yield 70%). LCMS (m/z): 194.1 (M+1). Under a N2 atmosphere the reaction mixture was heated at reflux temperature for 16 h The solvent was then removed the residue dissolved in ethyl acetate washed with water The separated organic layer was concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(2-methoxyphenyl)morpholine (200 mg, 1.02 mmol) in CH2Cl2 (20 mL) was added BBr3 (1 mL) at 0° C. The mixture was stirred for 2 h at 0° C. The mixture was then added drop wise to ice-water (50 mL) and the mixture treated with CH2Cl2 (2×20 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4 and concentrated to give the yellow solid which was used in next step without further purification (165 mg Yield 80%). LCMS (m/z): 180.1 (M+1). The combined organic layers were washed with brine (30 mL) dried over Na2SO4 concentrated to give the yellow solid which was used in next step without further purification (165 mg Yield 80%)

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

Procedure: To a solution of 1-iodo-2-methoxybenzene (1 g, 4.28 mmol) in dioxane (10 mL) was added morpholine (446.8 mg, 5.12 mmol), Pd2(dba)3 (100 mg, 0.1 mmol), Xantphos (200 mg, 0.3 mmol) and t-BuONa (671 mg, 6.0 mmol). Under a N2 atmosphere the reaction mixture was heated at reflux temperature for 16 h. The solvent was then removed and the residue dissolved in ethyl acetate and washed with water. The separated organic layer was concentrated to give the crude product which was used in next step without further purification (578 mg Yield 70%). LCMS (m/z): 194.1 (M+1). Under a N2 atmosphere the reaction mixture was heated at reflux temperature for 16 h The solvent was then removed the residue dissolved in ethyl acetate washed with water The separated organic layer was concentrated