2-(N-ethylanilino)ethanol

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

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

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

Procedure: 55.7 g (0.34 mol) of N-ethyl-N-(2-hydroxylethyl)aniline was dissolved in 250 ml of anhydrous tetrahydrofuran, and 162 ml (1.2-fold equivalent weight) of a 2.5M hexane solution n-butyllithium was dropwise added thereto over a period of 30 minutes at 0° C. in an atmosphere of argon, followed by stirring at 0° C. for 30 minutes. Next, to the reaction solution obtained, 30.0 g (1.09-fold equivalent weight) of methoxymethyl chloride was dropwise added, and the solution was heated and refluxed for 12 hours, followed by cooling. The precipitate formed was removed by filtration, and thereafter the filtrate obtained was concentrated under reduced pressure. The oily residue thus obtained was distilled under reduced pressure to obtain 63 g of N-ethyl-N-[2-(methoxymethyl)oxyethyl]aniline (yield: 89%). Next, to the reaction solution obtained the solution was heated refluxed for 12 hours by cooling The precipitate formed was removed by filtration the filtrate obtained was concentrated under reduced pressure The oily residue thus obtained was distilled under reduced pressure

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

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

Procedure: 51.8 g of 2-(N-ethylanilino)ethanol and 31.7 g of triethylamine were dissolved in 300 ml of acetone. To this was added slowly 25 g of acetyl chloride while cooling the resulting reaction solution with ice water. The resulting solution was then stirred for 6 hours at room temperature for reaction. 200 ml of water was then poured into the solution. The organic layer was extracted with ethyl acetate and dried with sodium sulfate. The solvent was then distilled off under reduced pressure to obtain 64.9 g of 2-(N-ethylanilino)ethyl acetate. while cooling The organic layer was extracted with ethyl acetate dried with sodium sulfate The solvent was then distilled off under reduced pressure

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

Procedure: 51.8 g of 2-(N-ethylanilino)ethanol and 31.7 g of triethylamine were dissolved in 300 ml of acetone. To this was added slowly 25 g of acetyl chloride while cooling the resulting reaction solution with ice water. The resulting solution was then stirred for 6 hours at room temperature for reaction. 200 ml of water was then poured into the solution. The organic layer was extracted with ethyl acetate and dried with sodium sulfate. The solvent was then distilled off under reduced pressure to obtain 64.9 g of 2-(N-ethylanilino)ethyl acetate. while cooling The organic layer was extracted with ethyl acetate dried with sodium sulfate The solvent was then distilled off under reduced pressure

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

Procedure: Benzoyl chloride (7.8 mL, 66 mmol) was added dropwise to a stirring solution of (N-ethyl-N-(2-hydroxyethyl)aniline (10 g, 60 mmol) in THF (200 ML) containing triethyl amine (9.2 g, 66 mmol) at room temperature. The mixture formed a thick precipitate which was stirred for 18 hours and then poured into water (400 mL). The aqueous layer was extracted with ethyl acetate (3×200 mL). The combined organic extracts were washed successively with 1 molar hydrochloric acid (100 mL), saturated sodium bicarbonate (100 mL), water (100 mL), saturated sodium chloride (100 mL), dried over magnesium sulfate and the solvent was removed under reduced pressure to yield the product (16.4 g, 96% yield) as a dark green oil. The mixture formed a thick precipitate which The aqueous layer was extracted with ethyl acetate (3×200 mL) The combined organic extracts were washed successively with 1 molar hydrochloric acid (100 mL), saturated sodium bicarbonate (100 mL), water (100 mL), saturated sodium chloride (100 mL) dried over magnesium sulfate the solvent was removed under reduced pressure

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

Procedure: Benzoyl chloride (7.8 mL, 66 mmol) was added dropwise to a stirring solution of (N-ethyl-N-(2-hydroxyethyl)aniline (10 g, 60 mmol) in THF (200 ML) containing triethyl amine (9.2 g, 66 mmol) at room temperature. The mixture formed a thick precipitate which was stirred for 18 hours and then poured into water (400 mL). The aqueous layer was extracted with ethyl acetate (3×200 mL). The combined organic extracts were washed successively with 1 molar hydrochloric acid (100 mL), saturated sodium bicarbonate (100 mL), water (100 mL), saturated sodium chloride (100 mL), dried over magnesium sulfate and the solvent was removed under reduced pressure to yield the product (16.4 g, 96% yield) as a dark green oil. The mixture formed a thick precipitate which The aqueous layer was extracted with ethyl acetate (3×200 mL) The combined organic extracts were washed successively with 1 molar hydrochloric acid (100 mL), saturated sodium bicarbonate (100 mL), water (100 mL), saturated sodium chloride (100 mL) dried over magnesium sulfate the solvent was removed under reduced pressure

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

Procedure: 2-(N-ethyl-N-phenylamino)ethanol (10 g, 60 mmol) in CH2Cl2 (150 mL) was reacted with SOCl2 (8.8 mL, 121 mmol). The mixture was heated to reflux for one hour and quenched. The solvent was evaporated and the residue was purified by silica gel column chromatography to provide intermediate 15a (5.54 g, 30 mmol, 50%) as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 7.28 (m, 2H), 6.74 (m, 3H), 3.65 (m, 4H), 3.46 (q, J=7.2 Hz, 2H), 1.22 (t, J=7.2 Hz, 3H); HRMS (ESI, positive) m/z calcd. for C10H15ClN [M+H]+: 184.0893, found: 184.0836. The mixture was heated to reflux for one hour quenched The solvent was evaporated the residue was purified by silica gel column chromatography

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

Procedure: 2-(N-ethyl-N-phenylamino)ethanol (10 g, 60 mmol) in CH2Cl2 (150 mL) was reacted with SOCl2 (8.8 mL, 121 mmol). The mixture was heated to reflux for one hour and quenched. The solvent was evaporated and the residue was purified by silica gel column chromatography to provide intermediate 3a (5.54 g, 30 mmol, 50%) as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 7.28 (m, 2H), 6.74 (m, 3H), 3.65 (m, 4H), 3.46 (q, J=7.2 Hz, 2H), 1.22 (t, J=7.2 Hz, 3H); HRMS (ESI, positive) m/z calcd. for C10H15ClN [M+H]+: 184.0893, found: 184.0836. The mixture was heated to reflux for one hour quenched The solvent was evaporated the residue was purified by silica gel column chromatography

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

Procedure: 2-(N-ethyl-N-phenylamino)ethanol (10 g, 60 mmol) in CH2Cl2 (150 mL) was reacted with SOCl2 (8.8 mL, 121 mmol). The mixture was heated to reflux for one hour and quenched. The solvent was evaporated and the residue was purified by silica gel column chromatography to provide intermediate 3a (5.54 g, 30 mmol, 50%) as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 7.28 (m, 2H), 6.74 (m, 3H), 3.65 (m, 4H), 3.46 (q, J=7.2 Hz, 2H), 1.22 (t, J=7.2 Hz, 3H); HRMS (ESI, positive) m/z calcd. for C10H15ClN [M+H]+: 184.0893, found: 184.0836. The mixture was heated to reflux for one hour quenched The solvent was evaporated the residue was purified by silica gel column chromatography

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

Procedure: 1.3 g (18.56 mmol) sodium nitrite was added in small portions to 13.2 g conc. sulphuric acid and cooled to 0° C. and diluted with 4.8 ml propionic acid and 19.2 ml acetic acid. 3.0 g (18.45 mmol) 2-amino-4-chloro-1,3-thiazole-5-carbaldehyde were then added in small portions. The viscous reaction mixture was stirred for 2 hours at 0° C. This mixture was then added slowly to a solution of 3.2 g (18.56 mmol) 2-[ethyl(phenyl)amino]ethanol in 180 ml water, containing 6 ml sulphuric acid. After stirring for another 2 hours at room temperature, the obtained precipitate was filtered off, washed with water and dried at 40° C. in vacuum. After stirring for another 2 hours at room temperature the obtained precipitate was filtered off washed with water dried at 40° C. in vacuum