benzyl N,N'-di(propan-2-yl)carbamimidate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Malic acid monomethyl ester (Example 2A) was dissolved in DMF and one equivalent of O-benzyl-N,N'-diisopropylisourea was added. The reaction mixture was stirred at room temperature for about 17 hours. Methylene chloride was added to the mixture and the suspension was filtered to remove the diisopropylurea. The filtrate was further diluted with methylene chloride and washed with water, 10% aqueous sodium carbonate, water, and with brine and was dried over magnesium sulfate. After filtration and evaporation the monobenzyl monomethyl ester was obtained as an oil. the suspension was filtered to remove the diisopropylurea The filtrate was further diluted with methylene chloride washed with water, 10% aqueous sodium carbonate, water with brine and was dried over magnesium sulfate After filtration and evaporation the monobenzyl monomethyl ester was obtained as an oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a dry round bottomed flask, equipped with a magnetic stirrer, 13.22 g (80 mmol) of Phenylalanine is added to 18.75 g (80 mmol) of the oil, N,N′-diisopropyl-O-benzylisourea and stirred at room temperature for about one hour. After about one hour the volume of the reaction is increased by the addition of 350 mL of dry tetrahyrdofuran (THF), and stirred at room temperature for an additional 48 hours. The resultant mixture is then filtered in order to remove the by-product, diisopropylurea, and the THF is then evaporated from the filtrate at reduced pressure. The oil which remains is pumped under high vacuum for about 24 hours yielding the protected amino acid, benzyl 2-amino-3-phenylpropanoate, in pure enough form for subsequent steps. In a dry round bottomed flask, equipped with a magnetic stirrer stirred at room temperature for an additional 48 hours The resultant mixture is then filtered in order to remove the by-product, diisopropylurea the THF is then evaporated from the filtrate at reduced pressure The oil which remains is pumped under high vacuum for about 24 hours

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A neat solution of 18.6 mL (15g, 118.8 mmol) of 1,3-diisopropylcarbodiimide and 60 mg (0.6 mmol) of cuprous chloride was placed under a blanket of argon and then cooled to 0° C. in an ice bath. To this reaction mixture was added dropwise (via syringe) 12.9 mL (13.5 g, 124.7 mmol) of benzyl alcohol. The resultant green reaction mixture was allowed to stir at 0° C. overnight, filtered through celite (rinsing with hexane) and the filtrate then Kugelrohr distilled (105° C., 2 mm Hg) to give 2-benzyl-1,3-diisopropyl isourea as a clear, colorless oil. To a solution of 650 mg (4.7 mmol) of 4-hydroxybenzoic acid in 20 mL of tetrahydrofuran was added 1.1 g (4.7 mmol) of 2-benzyl-1,3-diisopropyl isourea. The reaction mixture was allowed to stir at ambient temperature overnight, filtered (rinsing with tetrahydrofuran) and then concentrated in vacuo. Purification by flash chromatography (silica, 25% ethyl acetate in hexane) gave the title compound as a white solid. PMR (CDCl3): δ 5.22 (1 H, s), 5.35 (2 H, s), 6.87 (2 H, d, J=8.8 Hz), 7.34-7.50 (5 H, m), 8.01 (2 H, d, J=8.8 Hz). filtered (rinsing with tetrahydrofuran) concentrated in vacuo Purification by flash chromatography (silica, 25% ethyl acetate in hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A neat solution of 18.6 mL (15g, 118.8 mmol) of 1,3-diisopropylcarbodiimide and 60 mg (0.6 mmol) of cuprous chloride was placed under a blanket of argon and then cooled to 0° C. in an ice bath. To this reaction mixture was added dropwise (via syringe) 12.9 mL (13.5 g, 124.7 mmol) of benzyl alcohol. The resultant green reaction mixture was allowed to stir at 0° C. overnight, filtered through celite (rinsing with hexane) and the filtrate then Kugelrohr distilled (105° C., 2 mm Hg) to give 2-benzyl-1,3-diisopropyl isourea as a clear, colorless oil. To a solution of 650 mg (4.7 mmol) of 4-hydroxybenzoic acid in 20 mL of tetrahydrofuran was added 1.1 g (4.7 mmol) of 2-benzyl-1,3-diisopropyl isourea. The reaction mixture was allowed to stir at ambient temperature overnight, filtered (rinsing with tetrahydrofuran) and then concentrated in vacuo. Purification by flash chromatography (silica, 25% ethyl acetate in hexane) gave the title compound as a white solid. PMR (CDCl3): δ 5.22 (1 H, s), 5.35 (2 H, s), 6.87 (2 H, d, J=8.8 Hz), 7.34-7.50 (5 H, m), 8.01 (2 H, d, J=8.8 Hz). filtered (rinsing with tetrahydrofuran) concentrated in vacuo Purification by flash chromatography (silica, 25% ethyl acetate in hexane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A neat solution of 18.6 mL (15g, 118.8 mmol) of 1,3-diisopropylcarbodiimide and 60 mg (0.6 mmol) of cuprous chloride was placed under a blanket of argon and then cooled to 0° C. in an ice bath. To this reaction mixture was added dropwise (via syringe) 12.9 mL (13.5 g, 124.7 mmol) of benzyl alcohol. The resultant green reaction mixture was allowed to stir at 0° C. overnight, filtered through celite (rinsing with hexane) and the filtrate then Kugelrohr distilled (105° C., 2 mm Hg) to give 2-benzyl-1,3-diisopropyl isourea as a clear, colorless oil. To a solution of 650 mg (4.7 mmol) of 4-hydroxybenzoic acid in 20 mL of tetrahydrofuran was added 1.1 g (4.7 mmol) of 2-benzyl-1,3-diisopropyl isourea. The reaction mixture was allowed to stir at ambient temperature overnight, filtered (rinsing with tetrahydrofuran) and then concentrated in vacuo. Purification by flash chromatography (silica, 25% ethyl acetate in hexane) gave the title compound as a white solid. PMR (CDCl3): δ 5.22 (1 H, s), 5.35 (2 H, s), 6.87 (2 H, d, J=8.8 Hz), 7.34-7.50 (5 H, m), 8.01 (2 H, d, J=8.8 Hz). filtered through celite (rinsing with hexane) the filtrate then Kugelrohr distilled (105° C., 2 mm Hg)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5-methyl-4-nitro-thiophene-2-carboxylic acid (1.0 g, 5.3 mmol) and 1,3-diisopropyl-2-benzylisourea (1.54 g, 6.4 mmol) in acetonitrile (25 mL) was stirred under an inert atmosphere and heated to reflux. After 48 hours the mixture was cooled, the solvent was removed under reduced pressure, and the residue was triturated in diethyl ether and cooled. The precipitate was filtered off and rinsed with cold ether. The filtrate and washings were combined, and rotary evaporated under reduced pressure. The resulting residue was dissolved in a minimum of ethyl acetate, and the solution was filtered through a column of silica gel, eluting with more ethyl acetate. The filtrate was rotary evaporated to dryness under reduced pressure to afford 1.2 g of 5-methyl-4-nitro-thiophene-2-carboxylic acid benzyl ester. A sample was chromatographed on silica gel in ether/petroleum ether 1:1, then recrystallized from ethanol to give product with a mp 57-58° C. heated to reflux After 48 hours the mixture was cooled the solvent was removed under reduced pressure the residue was triturated in diethyl ether cooled The precipitate was filtered off rinsed with cold ether rotary evaporated under reduced pressure The resulting residue was dissolved in a minimum of ethyl acetate the solution was filtered through a column of silica gel eluting with more ethyl acetate The filtrate was rotary evaporated to dryness under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A neat solution of 18.6 mL (15 g, 118.8 mmol) of 1,3-diisopropylcarbodiimide and 60 mg (0.6 mmol) of cuprous chloride was placed under a blanket of argon and then cooled to 0° C. in an ice bath. To this reaction mixture was added dropwise (via syringe) 12.9 mL (13.5 g, 124.7 mmol) of benzyl alcohol. The resultant green reaction mixture was allowed to stir at 0° C. overnight, filtered through celite (rinsing with hexane) and the filtrate then Kugelrohr distilled (105° C., 2mm Hg) to give 2-benzyl-1,3-diisopropyl isourea as a clear, colorless oil. To a solution of 650 mg (4.7 mmol) of 4-hydroxybenzoic acid in 20 mL of tetrahydrofuran was added 1.1 g (4.7 mmol) of 2-benzyl-1,3-diisopropyl isourea. The reaction mixture was allowed to stir at ambient temperature overnight, filtered (rinsing with tetrahydrofuran) and then concentrated in vacuo. Purification by flash chromatography (silica, 25% ethyl acetate in hexane) gave the title compound as a white solid. filtered (rinsing with tetrahydrofuran) concentrated in vacuo Purification by flash chromatography (silica, 25% ethyl acetate in hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A neat solution of 18.6 mL (15 g, 118.8 mmol) of 1,3-diisopropylcarbodiimide and 60 mg (0.6 mmol) of cuprous chloride was placed under a blanket of argon and then cooled to 0° C. in an ice bath. To this reaction mixture was added dropwise (via syringe) 12.9 mL (13.5 g, 124.7 mmol) of benzyl alcohol. The resultant green reaction mixture was allowed to stir at 0° C. overnight, filtered through celite (rinsing with hexane) and the filtrate then Kugelrohr distilled (105° C., 2mm Hg) to give 2-benzyl-1,3-diisopropyl isourea as a clear, colorless oil. To a solution of 650 mg (4.7 mmol) of 4-hydroxybenzoic acid in 20 mL of tetrahydrofuran was added 1.1 g (4.7 mmol) of 2-benzyl-1,3-diisopropyl isourea. The reaction mixture was allowed to stir at ambient temperature overnight, filtered (rinsing with tetrahydrofuran) and then concentrated in vacuo. Purification by flash chromatography (silica, 25% ethyl acetate in hexane) gave the title compound as a white solid. filtered (rinsing with tetrahydrofuran) concentrated in vacuo Purification by flash chromatography (silica, 25% ethyl acetate in hexane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A neat solution of 18.6 mL (15 g, 118.8 mmol) of 1,3-diisopropylcarbodiimide and 60 mg (0.6 mmol) of cuprous chloride was placed under a blanket of argon and then cooled to 0° C. in an ice bath. To this reaction mixture was added dropwise (via syringe) 12.9 mL (13.5 g, 124.7 mmol) of benzyl alcohol. The resultant green reaction mixture was allowed to stir at 0° C. overnight, filtered through celite (rinsing with hexane) and the filtrate then Kugelrohr distilled (105° C., 2mm Hg) to give 2-benzyl-1,3-diisopropyl isourea as a clear, colorless oil. To a solution of 650 mg (4.7 mmol) of 4-hydroxybenzoic acid in 20 mL of tetrahydrofuran was added 1.1 g (4.7 mmol) of 2-benzyl-1,3-diisopropyl isourea. The reaction mixture was allowed to stir at ambient temperature overnight, filtered (rinsing with tetrahydrofuran) and then concentrated in vacuo. Purification by flash chromatography (silica, 25% ethyl acetate in hexane) gave the title compound as a white solid. filtered through celite (rinsing with hexane) the filtrate then Kugelrohr distilled (105° C., 2mm Hg)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A neat solution of 18.6 mL (15 g, 118.8 mmol) of 1,3-diisopropylcarbodiimide and 60 mg (0.6 mmol) of cuprous chloride was placed under a blanket of argon and then cooled to 0° C. in an ice bath. To this reaction mixture was added dropwise (via syringe) 12.9 mL (13.5 g, 124.7 mmol) of benzyl alcohol. The resultant green reaction mixture was allowed to stir at 0° C. overnight, filtered through celite (rinsing with hexane) and the filtrate then Kugelrohr distilled (105° C., 2 mm Hg) to give 2-benzyl-1,3-diisopropyl isourea as a clear, colorless oil. To a solution of 650 mg (4.7 mmol) of 4-hydroxybenzoic acid in 20 mL of tetrahydrofuran was added 1.1 g (4.7 mmol) of 2-benzyl-1,3-diisopropyl isourea. The reaction mixture was allowed to stir at ambient temperature overnight, filtered (rinsing with tetrahydrofuran) and then concentrated in vacuo. Purification by flash chromatography (silica, 3 25% ethyl acetate in hexane) gave the title compound as a white solid. filtered (rinsing with tetrahydrofuran) concentrated in vacuo Purification by flash chromatography (silica, 3 25% ethyl acetate in hexane)