N-[(4-methoxyphenyl)methyl]cyclobutanimine

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

Procedure: A solution of thiazole (2.253 mL, 31.7 mmol) in anhydrous tetrahydrofuran (30 mL) at −78° C. was treated dropwise with 2.5M n-butyllithium in hexane (12.68 mL, 31.7 mmol) via an additional funnel while maintaining the reaction temperature below −70° C. The lithium species was stirred for about 10 minutes and added dropwise via cannula to a −78° C. solution of N-cyclobutylidene-1-(4-methoxyphenyl)methanamine (5.0 g, 26.4 mmol) and boron trifluoride diethyl etherate (6.70 mL, 52.8 mmol) in 4.0 molar anhydrous tetrahydrofuran in anhydrous toluene (100 mL). The reaction was stirred and allowed to warm to ambient temperature over 30 minutes. The reaction was quenched with saturated ammonium chloride, and product was extracted with ethyl acetate. The organics were washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 10% to 20% ethyl acetate in hexanes, to provide the title compound. MS DCI(+) m/z 275.1 [M+H]+. while maintaining the reaction temperature below −70° C The reaction was quenched with saturated ammonium chloride, and product was extracted with ethyl acetate The organics were washed with water and brine dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by flash chromatography on silica gel eluting with a gradient of 10% to 20% ethyl acetate in hexanes

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

Procedure: A solution of thiazole (2.253 mL, 31.7 mmol) in anhydrous tetrahydrofuran (30 mL) at −78° C. was treated dropwise with 2.5M n-butyllithium in hexane (12.68 mL, 31.7 mmol) via an additional funnel while maintaining the reaction temperature below −70° C. The lithium species was stirred for about 10 minutes and added dropwise via cannula to a −78° C. solution of N-cyclobutylidene-1-(4-methoxyphenyl)methanamine (5.0 g, 26.4 mmol) and boron trifluoride diethyl etherate (6.70 mL, 52.8 mmol) in 4.0 molar anhydrous tetrahydrofuran in anhydrous toluene (100 mL). The reaction was stirred and allowed to warm to ambient temperature over 30 minutes. The reaction was quenched with saturated ammonium chloride, and product was extracted with ethyl acetate. The organics were washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 10% to 20% ethyl acetate in hexanes, to provide the title compound. MS DCI(+) m/z 275.1 [M+H]+. while maintaining the reaction temperature below −70° C The reaction was quenched with saturated ammonium chloride, and product was extracted with ethyl acetate The organics were washed with water and brine dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by flash chromatography on silica gel eluting with a gradient of 10% to 20% ethyl acetate in hexanes

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

Procedure: A solution of thiazole (2.253 mL, 31.7 mmol) in anhydrous tetrahydrofuran (30 mL) at −78° C. was treated dropwise with 2.5M n-butyllithium in hexane (12.68 mL, 31.7 mmol) via an additional funnel while maintaining the reaction temperature below −70° C. The lithium species was stirred for about 10 minutes and added dropwise via cannula to a −78° C. solution of N-cyclobutylidene-1-(4-methoxyphenyl)methanamine (5.0 g, 26.4 mmol) and boron trifluoride diethyl etherate (6.70 mL, 52.8 mmol) in 4.0 molar anhydrous tetrahydrofuran in anhydrous toluene (100 mL). The reaction was stirred and allowed to warm to ambient temperature over 30 minutes. The reaction was quenched with saturated ammonium chloride, and product was extracted with ethyl acetate. The organics were washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 10% to 20% ethyl acetate in hexanes, to provide the title compound. MS DCI(+) m/z 275.1 [M+H]+. while maintaining the reaction temperature below −70° C The reaction was quenched with saturated ammonium chloride, and product was extracted with ethyl acetate The organics were washed with water and brine dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by flash chromatography on silica gel eluting with a gradient of 10% to 20% ethyl acetate in hexanes

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

Procedure: A solution of (4-methoxyphenyl)methanamine (9.26 mL, 71.3 mmol) and cyclobutanone (5.35 mL, 71.3 mmol) in anhydrous ethyl ether (70 mL) was treated with activated 4 angstrom molecular sieves (2.5 g). The mixture was stirred vigorously for 16 hours at ambient temperature. The reaction mixture was filtered, and the sieves were washed with ethyl ether. The filtrate was concentrated under reduced pressure with no heat. The title compound was stored under nitrogen and used without further purification. MS DCI(+) m/z 190.3 [M+H]+. The reaction mixture was filtered the sieves were washed with ethyl ether The filtrate was concentrated under reduced pressure with no heat used without further purification