(2-bromo-3-methylphenyl)-morpholin-4-ylmethanone

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

Procedure: A solution of 2,3-dihydrofuran (0.70 mL, 9.25 mmol) in THF (9.0 mL) under inert atmosphere was cooled to −78° C. A solution of n-butyllithium, 1.7 M in pentanes (5.98 mL, 10.17 mmol), was added dropwise over 10 min. The reaction was maintained at that temperature for 30 min, and allowed to warm to 0° C. for 30 min. It was cooled back down to −78° C. and then added via cannula to a solution of (2-bromo-3-methylphenyl)(morpholino)methanone (2.02 g, 7.12 mmol) in Et2O (17.92 mL), also at −78° C. The solution was stirred at that temperature for 10 min and then allowed to warm to 0° C. The mixture was partitioned between Et2O and water and the organics were washed with water and brine. The solution was dried over Na2SO4 and concentrated. The crude material was absorbed onto a plug of silica gel and purified by column chromatography eluting with a gradient of Et2O in hexane, to provide (2-bromo-3-methylphenyl)(4,5-dihydrofuran-2-yl)methanone as a colorless oil. This oil was immediately re-dissolved in Et2O and placed under nitrogen before storing in the freezer for further use. The reaction was maintained at that temperature for 30 min It was cooled back down to −78° C. to warm to 0° C The mixture was partitioned between Et2O and water the organics were washed with water and brine The solution was dried over Na2SO4 concentrated The crude material was absorbed onto a plug of silica gel purified by column chromatography eluting with a gradient of Et2O in hexane

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

Procedure: A solution of 2-bromo-3-methylbenzoic acid (2.19 g, 10.18 mmol) in THF (20.37 mL) was treated with N,N′-carbonyldiimidazole (1.98 g, 12.2 mmol). The reaction mixture was stirred at ambient temperature overnight (14 h). Morpholine (3.11 mL, 35.6 mmol) was added in one portion. The resulting solution was stirred for 8 h and then partitioned between EtOAc and water. Organic layer washed with water, dilute HCl, saturated aqueous Na2CO3, water and brine. The solution was then concentrated in vacuo to afford (2-bromo-3-methylphenyl)(morpholino)methanone as a white crystalline solid. The resulting solution was stirred for 8 h partitioned between EtOAc and water Organic layer washed with water, dilute HCl, saturated aqueous Na2CO3, water and brine The solution was then concentrated in vacuo

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

Procedure: A solution of 2,3-dihydrofuran (0.70 mL, 9.25 mmol) in THF (9.0 mL) under inert atmosphere was cooled to −78° C. A solution of n-butyllithium, 1.7 M in pentanes (5.98 mL, 10.17 mmol), was added dropwise over 10 min. The reaction was maintained at that temperature for 30 min, and allowed to warm to 0° C. for 30 min. It was cooled back down to −78° C. and then added via cannula to a solution of (2-bromo-3-methylphenyl)(morpholino)methanone (2.02 g, 7.12 mmol) in Et2O (17.92 mL), also at −78° C. The solution was stirred at that temperature for 10 min and then allowed to warm to 0° C. The mixture was partitioned between Et2O and water and the organics were washed with water and brine. The solution was dried over Na2SO4 and concentrated. The crude material was absorbed onto a plug of silica gel and purified by column chromatography eluting with a gradient of Et2O in hexane, to provide (2-bromo-3-methylphenyl)(4,5-dihydrofuran-2-yl)methanone as a colorless oil. This oil was immediately re-dissolved in Et2O and placed under nitrogen before storing in the freezer for further use. The reaction was maintained at that temperature for 30 min It was cooled back down to −78° C. to warm to 0° C The mixture was partitioned between Et2O and water the organics were washed with water and brine The solution was dried over Na2SO4 concentrated The crude material was absorbed onto a plug of silica gel purified by column chromatography eluting with a gradient of Et2O in hexane

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

Procedure: A solution of 2-bromo-3-methylbenzoic acid (2.19 g, 10.18 mmol) in THF (20.37 mL) was treated with N,N′-carbonyldiimidazole (1.98 g, 12.2 mmol). The reaction mixture was stirred at ambient temperature overnight (14 h). Morpholine (3.11 mL, 35.6 mmol) was added in one portion. The resulting solution was stirred for 8 h and then partitioned between EtOAc and water. Organic layer washed with water, dilute HCl, saturated aqueous Na2CO3, water and brine. The solution was then concentrated in vacuo to afford (2-bromo-3-methylphenyl)(morpholino)methanone as a white crystalline solid. The resulting solution was stirred for 8 h partitioned between EtOAc and water Organic layer washed with water, dilute HCl, saturated aqueous Na2CO3, water and brine The solution was then concentrated in vacuo