N,N-diethyl-3-methylbut-2-enamide

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 250 mL round bottomed flask a solution of lithiumisopropylcyclohexylamide was prepared from isopropylcyclohexylamine (6.21 g, 7.23 mL, 44 mmol) in THF (50 mL) and butyllithium (2.5M in hexane, 17.6 mL, 44 mmol). The solution was cooled to -78° C. under nitrogen and N,N-diethyl-3,3-dimethylacrylamide [109] (3.10 g, 20 mmol) in THF (20 mL) was added. After stirring for 30 min at -78° C., the solution was warmed to room temperature and stirred for 5 h. The reaction mixture was then cooled to -78° C., and 1,4-dibromoanisole [112] (5.852 g, 22 mmol) in THF (30 mL) was added via syringe. The solution was stirred at 0° C. for 24 h and then quenched with saturated aqueous ammonium chloride (100 mL) and diluted with ether (30 mL). The organic layer was separated and the aqueous layer was extracted with ether (3×40 mL). The combined organic layers were washed with brine (40 mL), dried with sodium sulfate and concentrated in vacuo to give 4.60 g of crude material. Flash chromatography of the crude material (hexane/ethyl acetate; 9:1) yielded product 113 (1.17 g, 22%) as a light yellow oil. the solution was warmed to room temperature stirred for 5 h The reaction mixture was then cooled to -78° C. The solution was stirred at 0° C. for 24 h quenched with saturated aqueous ammonium chloride (100 mL) diluted with ether (30 mL) The organic layer was separated the aqueous layer was extracted with ether (3×40 mL) The combined organic layers were washed with brine (40 mL) dried with sodium sulfate concentrated in vacuo to give 4.60 g of crude material

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

Procedure: To a stirred solution of isopropylcyclohexylamine (7.5 mL, 0.45 mmol) in 60 mL of THF at -78° C. under N2 was added n-BuLi (20.0 mL, 50.0 mmol, 2.5M in hexanes). The mixture was stirred for 20 min, warmed to 0° C., and then stirred for 1 h. The mixture was cooled to -78° C. and solution of N,N-diethyl-3,3-dimethylacrylamide (2.10 g, 13.0 mmol) in 40 mL of THF was added. This mixture was stirred at -78° C. for 1 h. The cold bath was removed and the reaction mixture was allowed to warm to -20° C. over a period of 10 min. A solution of 2,4-dibromo-1-methoxymethoxybenzene (9) in 30 mL of THF was added. The reaction mixture was stirred overnight at room temperature, and then quenched with saturated NH4Cl Et2O was added and the solution was washed with H2O, brine, dried over Na2SO4, and concentrated in vacuo. The crude product was purified by flash chromatography (hexanes/EtOAc; 9:1) to yield napthol 12 (1.15 g, 29%) as a brown oil; 1H NMR (CDCl3, 300 MHz): δ9.31 [s, OH], 7.54 [d, J=8.4 Hz, ArH(6)], 7.49 [s, ArH(4)], 6.82 [s, ArH(2)[, 6.81 [d, J=8.4 Hz, ArH(7)], 5.46 [s, OCH2OCH3 ], 3.55 [s, OCH3 ], and 2.47 [s, ARCH3 (3)]; 13C NMR (CDCl3, 75 MHz): 67 154.3, 153.5, 139.5, 134.5, 129.6, 118.2, 115.5, 114.5, 113.6, 107.3, 95.9, 56.9, and 22.0; LRMS (EI): m/z 298 (M+, 13), 296 (M+, 11), 128 (5), 115 (9), and 45 (100). stirred for 1 h The mixture was cooled to -78° C. This mixture was stirred at -78° C. for 1 h The cold bath was removed to warm to -20° C. over a period of 10 min A solution of 2,4-dibromo-1-methoxymethoxybenzene (9) in 30 mL of THF was added The reaction mixture was stirred overnight at room temperature quenched with saturated NH4Cl Et2O was added the solution was washed with H2O, brine dried over Na2SO4 concentrated in vacuo The crude product was purified by flash chromatography (hexanes/EtOAc; 9:1)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 250 mL round bottomed flask a solution of lithiumisopropylcyclohexylamide was prepared from isopropylcyclohexylamine (6.21 g, 7.23 mL, 44 mmol) in THF (50 mL) and butyllithium (2.5M in hexane, 17.6 mL, 44 mmol). The solution was cooled to -78° C. under nitrogen and N,N-diethyl-3,3-dimethylacrylamide [109] (3.10 g, 20 mmol) in THF (20 mL) was added. After stirring for 30 min at -78° C., the solution was warmed to room temperature and stirred for 5 h. The reaction mixture was then cooled to -78° C., and 1,4-dibromoanisole [112] (5.852 g, 22 mmol) in THF (30 mL) was added via syringe. The solution was stirred at 0° C. for 24 h and then quenched with saturated aqueous ammonium chloride (100 mL) and diluted with ether (30 mL). The organic layer was separated and the aqueous layer was extracted with ether (3×40 mL). The combined organic layers were washed with brine (40 mL), dried with sodium sulfate and concentrated in vacuo to give 4.60 g of crude material. Flash chromatography of the crude material (hexane/ethyl acetate; 9:1) yielded product 113 (1.17 g, 22%) as a light yellow oil. the solution was warmed to room temperature stirred for 5 h The reaction mixture was then cooled to -78° C. The solution was stirred at 0° C. for 24 h quenched with saturated aqueous ammonium chloride (100 mL) diluted with ether (30 mL) The organic layer was separated the aqueous layer was extracted with ether (3×40 mL) The combined organic layers were washed with brine (40 mL) dried with sodium sulfate concentrated in vacuo to give 4.60 g of crude material

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

Procedure: To a stirred solution of isopropylcyclohexylamine (7.5 mL, 0.45 mmol) in 60 mL of THF at -78° C. under N2 was added n-BuLi (20.0 mL, 50.0 mmol, 2.5M in hexanes). The mixture was stirred for 20 min, warmed to 0° C., and then stirred for 1 h. The mixture was cooled to -78° C. and solution of N,N-diethyl-3,3-dimethylacrylamide (2.10 g, 13.0 mmol) in 40 mL of THF was added. This mixture was stirred at -78° C. for 1 h. The cold bath was removed and the reaction mixture was allowed to warm to -20° C. over a period of 10 min. A solution of 2,4-dibromo-1-methoxymethoxybenzene (9) in 30 mL of THF was added. The reaction mixture was stirred overnight at room temperature, and then quenched with saturated NH4Cl Et2O was added and the solution was washed with H2O, brine, dried over Na2SO4, and concentrated in vacuo. The crude product was purified by flash chromatography (hexanes/EtOAc; 9:1) to yield napthol 12 (1.15 g, 29%) as a brown oil; 1H NMR (CDCl3, 300 MHz): δ9.31 [s, OH], 7.54 [d, J=8.4 Hz, ArH(6)], 7.49 [s, ArH(4)], 6.82 [s, ArH(2)[, 6.81 [d, J=8.4 Hz, ArH(7)], 5.46 [s, OCH2OCH3 ], 3.55 [s, OCH3 ], and 2.47 [s, ARCH3 (3)]; 13C NMR (CDCl3, 75 MHz): 67 154.3, 153.5, 139.5, 134.5, 129.6, 118.2, 115.5, 114.5, 113.6, 107.3, 95.9, 56.9, and 22.0; LRMS (EI): m/z 298 (M+, 13), 296 (M+, 11), 128 (5), 115 (9), and 45 (100). stirred for 1 h The mixture was cooled to -78° C. This mixture was stirred at -78° C. for 1 h The cold bath was removed to warm to -20° C. over a period of 10 min A solution of 2,4-dibromo-1-methoxymethoxybenzene (9) in 30 mL of THF was added The reaction mixture was stirred overnight at room temperature quenched with saturated NH4Cl Et2O was added the solution was washed with H2O, brine dried over Na2SO4 concentrated in vacuo The crude product was purified by flash chromatography (hexanes/EtOAc; 9:1)