4-[(5-bromofuran-2-yl)methyl]morpholine

Conditions: temp:0.00; pressure:0.00; stir:

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: To a mixture of 5-bromo-2-furaldehyde (1.76 g) and morpholine (1.00 ml) in 40 mL anhydrous THF at room temperature was added acetic acid (0.60 mL) followed by sodium triacetoxyborohydride (3.28 g). The mixture was stirred at room temperature for 3 h and then poured into a saturated solution of sodium bicarbonate (100 mL). After stirring vigorously for 5 min the layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated to dryness. Purification of the residue by flash chromatography afforded 2.09 g (8.49 mmol, 84% yield) of 4-(5-bromo-2-furylmethyl)morpholine. After stirring vigorously for 5 min the layers were separated the aqueous layer was extracted with EtOAc The combined organic layers were washed with brine dried (Na2SO4) filtered evaporated to dryness Purification of the residue by flash chromatography

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

Procedure: To a mixture of 5-bromo-2-furaldehyde (1.76 g) and morpholine (1.00 ml) in 40 mL anhydrous THF at room temperature was added acetic acid (0.60 mL) followed by sodium triacetoxyborohydride (3.28 g). The mixture was stirred at room temperature for 3 h and then poured into a saturated solution of sodium bicarbonate (100 mL). After stirring vigorously for 5 min the layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated to dryness. Purification of the residue by flash chromatography afforded 2.09 g (8.49 mmol, 84% yield) of 4-(5-bromo-2-furylmethyl)morpholine. After stirring vigorously for 5 min the layers were separated the aqueous layer was extracted with EtOAc The combined organic layers were washed with brine dried (Na2SO4) filtered evaporated to dryness Purification of the residue by flash chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A three necked flask was charged with methyl 4-bromo-3-methylbenzoate (2.18 mmol), bis(pinacolato)diboron (2.29 mmol), palladium acetate (0.065 mmol), potassium acetate (6.54 mmol) and DMF (10 ml). The solution was degassed by bubbling through N2 gas for 30 mins and was then heated to 80° C. under N2 for 3 h. Reaction was then cooled to room temperature and 4-(5-Bromo-furan-2-ylmethyl)-morpholine (2.18 mmol), cesium carbonate (3.27 mmol) and Pd(PPh3)4 (0.065 mmol) added. The reaction was heated to 80° C. and stirred for a further 17 h. Mixture was then diluted with EtOAc and water and filtered through a celite pad to remove black particulates. The organic layer was separated, washed with brine and dried over Na2SO4 and concentrated in vacuo. Flash chromatography of the residue (silica, 10-99% EtOAc in hexane) gave 3-Methyl-4-(5-morpholin-4-ylmethyl-furan-2-yl)-benzoic acid methyl ester as a grey powdery solid: m/z in MS ES+=316 [M+H]+, 0.51 mmol, 23%. The solution was degassed by bubbling through N2 gas for 30 mins Reaction was then cooled to room temperature The reaction was heated to 80° C. filtered through a celite pad to remove black particulates The organic layer was separated washed with brine dried over Na2SO4 concentrated in vacuo

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

Procedure: To a mixture of 5-bromo-2-furaldehyde (1.76 g) and morpholine (1.00 ml) in 40 mL anhydrous THF at room temperature was added acetic acid (0.60 mL) followed by sodium triacetoxyborohydride (3.28 g). The mixture was stirred at room temperature for 3 h and then poured into a saturated solution of sodium bicarbonate (100 mL). After stirring vigorously for 5 min the layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated to dryness. Purification of the residue by flash chromatography afforded 2.09 g (8.49 mmol, 84% yield) of 4-(5-bromo-2-furylmethyl)morpholine. After stirring vigorously for 5 min the layers were separated the aqueous layer was extracted with EtOAc The combined organic layers were washed with brine dried (Na2SO4) filtered evaporated to dryness Purification of the residue by flash chromatography

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

Procedure: To a mixture of 5-bromo-2-furaldehyde (1.76 g) and morpholine (1.00 ml) in 40 mL anhydrous THF at room temperature was added acetic acid (0.60 mL) followed by sodium triacetoxyborohydride (3.28 g). The mixture was stirred at room temperature for 3 h and then poured into a saturated solution of sodium bicarbonate (100 mL). After stirring vigorously for 5 min the layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated to dryness. Purification of the residue by flash chromatography afforded 2.09 g (8.49 mmol, 84% yield) of 4-(5-bromo-2-furylmethyl)morpholine. After stirring vigorously for 5 min the layers were separated the aqueous layer was extracted with EtOAc The combined organic layers were washed with brine dried (Na2SO4) filtered evaporated to dryness Purification of the residue by flash chromatography

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A three necked flask was charged with methyl 4-bromo-3-methylbenzoate (2.18 mmol), bis(pinacolato)diboron (2.29 mmol), palladium acetate (0.065 mmol), potassium acetate (6.54 mmol) and DMF (10 ml). The solution was degassed by bubbling through N2 gas for 30 mins and was then heated to 80° C. under N2 for 3 h. Reaction was then cooled to room temperature and 4-(5-Bromo-furan-2-ylmethyl)-morpholine (2.18 mmol), cesium carbonate (3.27 mmol) and Pd(PPh3)4 (0.065 mmol) added. The reaction was heated to 80° C. and stirred for a further 17 h. Mixture was then diluted with EtOAc and water and filtered through a celite pad to remove black particulates. The organic layer was separated, washed with brine and dried over Na2SO4 and concentrated in vacuo. Flash chromatography of the residue (silica, 10-99% EtOAc in hexane) gave 3-Methyl-4-(5-morpholin-4-ylmethyl-furan-2-yl)-benzoic acid methyl ester as a grey powdery solid: m/z in MS ES+=316 [M+H]+, 0.51 mmol, 23%. The solution was degassed by bubbling through N2 gas for 30 mins Reaction was then cooled to room temperature The reaction was heated to 80° C. filtered through a celite pad to remove black particulates The organic layer was separated washed with brine dried over Na2SO4 concentrated in vacuo