ethyl 2-(propan-2-ylamino)acetate

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

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

Procedure: Propan-2-amine (2001) (59 g, 1.0 mol) and ethyl chloroacetate (122 g, 1.0 mol) were dissolved in toluene (200 mL) and the mixture was stirred at reflux for 2 h. The reaction mixture was allowed to cool to RT, poured into ice-water (500 mL) and extracted with ethyl acetate (3×250 mL). The combined organic layer was washed with brine (50 mL), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (10-50% EA/PE) to afford the product, ethyl 2-(isopropylamino)acetate (2002) (70 g, 51% yield) as an oil. at reflux for 2 h extracted with ethyl acetate (3×250 mL) The combined organic layer was washed with brine (50 mL) dried over Na2SO4 filtered The filtrate was concentrated in vacuo the residue was purified by flash column chromatography on silica gel (10-50% EA/PE)

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

Procedure: Methyl 6-chloro-5-nitronicotinate (2 g, 9.23 mmol) was added to ethyl 2-(isopropylamino)acetate (5.0 g, 34.5 mmol) neat while stirring at room temperature. The viscous yellow reaction was heated to 90° C. for one h and then allowed to cool back to room temperature. The reaction was diluted with dichloromethane (20 mL) and purified via column chromatography (220 g SiO2, 20-30% gradient, ethyl acetate in hexanes) to yield the title compound (2.39 g, 83%) as a yellow oil. [M+H] calc'd for C14H19N3O6, 326. found, 326. The viscous yellow reaction was heated to 90° C. for one h to cool back to room temperature purified via column chromatography (220 g SiO2, 20-30% gradient, ethyl acetate in hexanes)

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

Procedure: Methyl 6-chloro-5-nitronicotinate (2 g, 9.23 mmol) was added to ethyl 2-(isopropylamino)acetate (5.0 g, 34.5 mmol) neat while stirring at room temperature. The viscous yellow reaction was heated to 90° C. for one h and then allowed to cool back to room temperature. The reaction was diluted with dichloromethane (20 mL) and purified via column chromatography (220 g SiO2, 20-30% gradient, ethyl acetate in hexanes) to yield the title compound (2.39 g, 83%) as a yellow oil. [M+H] calc'd for C14H19N3O6, 326. found, 326. The viscous yellow reaction was heated to 90° C. for one h to cool back to room temperature purified via column chromatography (220 g SiO2, 20-30% gradient, ethyl acetate in hexanes)

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

Procedure: To a suspension of ethyl 2-aminoacetate hydrochloride (20 g, 143.28 mmol) in THF (400 mL) was added glacial acetic acid (20 mL) followed by acetone (11.59 mL, 151.62 mmol). The reaction was stirred 30 min at room temperature. Sodium triacetoxyborohydride (60.73 g, 286.56 mmol) was added over the course of one hour. The reaction was poured slowly into a vigorously stirred biphasic mixture of water (300 mL) and ethyl acetate (800 mL). The aqueous layer was adjusted to pH 13 using a solution of 50% (weight) NaOH. The mixture was stirred 30 min and poured into a separatory funnel. The organic layer was collected and the aqueous layer was back extracted with ethyl acetate (3×200 mL). The organic layers were combined, washed with brine (300 mL), dried with sodium sulfate, and concentrated to yield the title compound (17.6 g, 85%) as a translucent oil which was used in the next step without further purification. [M+H] calc'd for C7H15NO2, 146. found, 146. The mixture was stirred 30 min poured into a separatory funnel The organic layer was collected the aqueous layer was back extracted with ethyl acetate (3×200 mL) washed with brine (300 mL) dried with sodium sulfate concentrated

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

Procedure: A mixture of 5 parts of phenyl[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]carbamate, 3 parts of ethyl[(1-methylethyl)amino]acetate, 1 part of N,N-dimethyl-4-pyridinamine and 100 parts of 1,4-dioxane was stirred and refluxed overnight. The warm solution was saturated with water and allowed to cool. The solution was poured onto water and extracted with trichloromethane. The extract was washed with water, dried, filtered and evaporated. The residue was purified by filtration over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The filtrate was evaporated and the residue was crystallized from methylbenzene, yielding 3.7 parts (73%) of 3-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-1-(1-methylethyl)-2,4-imidazolidinedione; mp. 193.7° C. (38). refluxed overnight to cool The solution was poured onto water extracted with trichloromethane The extract was washed with water dried filtered evaporated The residue was purified by filtration over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent The filtrate was evaporated the residue was crystallized from methylbenzene

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

Procedure: At room temperature, 3-Bromo-6-chloro-3-(3-chloro-benzyl)-1,3-dihydro-indol-2-one (4.57 g, 12.3 mmol) and Isopropylamino-acetic acid ethyl ester (2.15 g, 14.8 mmol), DIPEA (2.14 ml) were mixed in about 40 ml dichloromethane. After stirred for about 3 h, the solution was concentrated and the crude product was purified by chromatography to obtain 4.7 g solid rac-{[6-Chloro-3-(3-chloro-benzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-isopropyl-amino}-acetic acid ethyl ester. MS: 435 (M+H)+. the solution was concentrated the crude product was purified by chromatography

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

Procedure: At room temperature, 3-Bromo-6-chloro-3-(3-chloro-benzyl)-1,3-dihydro-indol-2-one (4.57 g, 12.3 mmol) and Isopropylamino-acetic acid ethyl ester (2.15 g, 14.8 mmol), DIPEA (2.14 ml) were mixed in about 40 ml dichloromethane. After stirred for about 3 h, the solution was concentrated and the crude product was purified by chromatography to obtain 4.7 g solid rac-{[6-Chloro-3-(3-chloro-benzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-isopropyl-amino}-acetic acid ethyl ester. MS: 435 (M+H)+. the solution was concentrated the crude product was purified by chromatography

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

Procedure: A 250 milliliter round-bottom, 3-neck flask was equipped with a condenser, a thermometer, a dropping funnel, and a Teflon® spin-bar magnet for stirring. The outlets were protected from moisture by calcium chloride drying tubes, and the flask was immersed in an ice-water cooling mixture. The flask was charged with an 80 milliliter dichloromethane solution containing 0.015 mole (2.2 grams) of the ethyl N-isopropylaminoacetate (described above) and 0.015 mole (1.5 grams) of triethylamine. The solution was stirred while cooling in an ice-water bath. A 20 milliliter solution of dichloromethane containing 0.015 mole (3.14 grams) of 3,5-dichlorobenzoylchloride was added dropwise over a period of 1.0 hour with stirring and the stirring was continued for several hours followed by allowing the mixture to warm to room temperature. The reaction solution was washed four times with water (25 milliliters) to remove the triethylamine hydrochloride. The washed organic solution was filtered to remove the phase water and concentrated first by rotary evaporation (house vacuum, water bath to 65° C.) to 4.9 grams of a dull yellow syrup (nD20 1.5257) and then, using a vacuum pump (<1 mm, oil bath to 50° to 60° C.) for 1.0 hour, to 4.5 grams (94 percent crude yield) nD20 (1.5280) ethyl N-3,5-dichlorobenzoyl-N-isopropylaminoacetate. It had a mass spectra (m/e) of molecular weight of 317, an infrared spectra (neat) mull technique with ester C=O band at 1745 centimeters-1 and amide (C=O) band at 1635 centimeters-1. It had the following nuclear magnetic resonance values δ (CDCl3) of 1.1 (doublet, 6H, (CH3)2C--), 1.3 (triplet, 3H, CH3--), 3.7-4.5 (4.0 broad singlet, 4.2 quartet, (overlap), 5H, CH2N, CH2, CH (heptet obscured)), and 7.3-7.5 (multiplets, 3H, aromatic). A 250 milliliter round-bottom, 3-neck flask was equipped with a condenser while cooling in an ice-water bath with stirring the stirring was continued for several hours The reaction solution was washed four times with water (25 milliliters) to remove the triethylamine hydrochloride The washed organic solution was filtered to remove the phase water concentrated first by rotary evaporation (house vacuum, water bath to 65° C.) to 4.9 grams of a dull yellow syrup (nD20 1.5257) a vacuum pump (<1 mm, oil bath to 50° to 60° C.) for 1.0 hour

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

Procedure: Propan-2-amine (2001)(59 g, 1.0 mol) and ethyl chloroacetate (122 g, 1.0 mol) were dissolved in toluene (200 mL and the mixture was stirred at reflux for 2 h. The reaction mixture was allowed to cool to RT, poured into ice-water (500 mL) and extracted with ethyl acetate (3×250 mL). The combined organic layer was washed with brine (50 mL), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (10-50% EA/PE) to afford the product, ethyl 2-(isopropylamino)acetate (2002) (70 g, 51% yield) as an oil. at reflux for 2 h extracted with ethyl acetate (3×250 mL) The combined organic layer was washed with brine (50 mL) dried over Na2SO4 filtered The filtrate was concentrated in vacuo the residue was purified by flash column chromatography on silica gel (10-50% EA/PE)

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

Procedure: A 250 milliliter round-bottom, 3-neck flask was equipped with a condenser, a thermometer, a dropping funnel, and a Teflon® spin-bar magnet for stirring. The outlets were protected from moisture by calcium chloride drying tubes, and the flask was immersed in an ice-water cooling mixture. The flask was charged with an 80 milliliter dichloromethane solution containing 0.015 mole (2.2 grams) of the ethyl N-isopropylaminoacetate (described above) and 0.015 mole (1.5 grams) of triethylamine. The solution was stirred while cooling in an ice-water bath. A 20 milliliter solution of dichloromethane containing 0.015 mole (3.14 grams) of 3,5-dichlorobenzoylchloride was added dropwise over a period of 1.0 hour with stirring and the stirring was continued for several hours followed by allowing the mixture to warm to room temperature. The reaction solution was washed four times with water (25 milliliters) to remove the triethylamine hydrochloride. The washed organic solution was filtered to remove the phase water and concentrated first by rotary evaporation (house vacuum, water bath to 65° C.) to 4.9 grams of a dull yellow syrup (nD20 1.5257) and then, using a vacuum pump (<1 mm, oil bath to 50° to 60° C.) for 1.0 hour, to 4.5 grams (94 percent crude yield) nD20 (1.5280) ethyl N-3,5-dichlorobenzoyl-N-isopropylaminoacetate. It had a mass spectra (m/e) of molecular weight of 317, an infrared spectra (neat) mull technique with ester C=O band at 1745 centimeters-1 and amide (C=O) band at 1635 centimeters-1. It had the following nuclear magnetic resonance values δ (CDCl3) of 1.1 (doublet, 6H, (CH3)2C--), 1.3 (triplet, 3H, CH3--), 3.7-4.5 (4.0 broad singlet, 4.2 quartet, (overlap), 5H, CH2N, CH2, CH (heptet obscured)), and 7.3-7.5 (multiplets, 3H, aromatic). A 250 milliliter round-bottom, 3-neck flask was equipped with a condenser while cooling in an ice-water bath with stirring the stirring was continued for several hours The reaction solution was washed four times with water (25 milliliters) to remove the triethylamine hydrochloride The washed organic solution was filtered to remove the phase water concentrated first by rotary evaporation (house vacuum, water bath to 65° C.) to 4.9 grams of a dull yellow syrup (nD20 1.5257) a vacuum pump (<1 mm, oil bath to 50° to 60° C.) for 1.0 hour

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

Procedure: Propan-2-amine (2001)(59 g, 1.0 mol) and ethyl chloroacetate (122 g, 1.0 mol) were dissolved in toluene (200 mL and the mixture was stirred at reflux for 2 h. The reaction mixture was allowed to cool to RT, poured into ice-water (500 mL) and extracted with ethyl acetate (3×250 mL). The combined organic layer was washed with brine (50 mL), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (10-50% EA/PE) to afford the product, ethyl 2-(isopropylamino)acetate (2002) (70 g, 51% yield) as an oil. at reflux for 2 h extracted with ethyl acetate (3×250 mL) The combined organic layer was washed with brine (50 mL) dried over Na2SO4 filtered The filtrate was concentrated in vacuo the residue was purified by flash column chromatography on silica gel (10-50% EA/PE)