benzyl (2R)-2-amino-3-methylbutanoate

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

実験手順: To a solution of D-valine benzyl ester free base (12.92 g, 62 mmol) in dry methylene chloride (120 mL) was added 3,4-(methylenedioxy)phenyl methanol (9.45 g, 62 mmol) and sodium triacetoxyborohydride (18.50 g, 86.8 mmol). After 15 h, the reaction mixture was quenched with saturated aqueous sodium bicarbonate (120 mL) and the aqueous layer was separated and extracted with methylene chloride. The combined methylene chloride layers were washed with brine, dried over magnesium sulfate, and concentrated. The residue was chromatographed (300 g SiO2, 5% ethyl acetate-hexanes) to afford 2(R)-(3,4-methylenedioxy-benzylamino)-3-methylbutyric acid benzyl ester (18 g) as a colorless oil. the reaction mixture was quenched with saturated aqueous sodium bicarbonate (120 mL) the aqueous layer was separated extracted with methylene chloride The combined methylene chloride layers were washed with brine dried over magnesium sulfate concentrated The residue was chromatographed (300 g SiO2, 5% ethyl acetate-hexanes)

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

実験手順: To a solution of D-valine benzyl ester (4 g, 19.3 mmol) and trimethylsilylcyanide (7.2 mL, 57.9 mmol) in acetonitrile (40 mL) was added 4-methoxy-2,3,6-trimethylbenzenesulfonyl chloride (4.8 g, 19.3 mmol). After 3 h, the reaction mixture was diluted with ethyl acetate (100 mL) and transferred to a separatory funnel. Aqueous hydrochloric acid (120 mL, 2.5%) was added and the organic layer was separated and washed with 5% sodium bicarbonate and brine and then dried over magnesium sulfate. The organics were removed in vacuo to give 2(R)-(4-methoxy-2,3,6-trimethylbenzenesulfonylamino)-3-methylbutyric acid benzyl ester (8 g) as a brown oil. transferred to a separatory funnel the organic layer was separated washed with 5% sodium bicarbonate and brine dried over magnesium sulfate The organics were removed in vacuo

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

実験手順: To a solution of D-valine benzyl ester (4 g, 19.3 mmol) and trimethylsilylcyanide (7.2 mL, 57.9 mmol) in acetonitrile (40 mL) was added 4-methoxy-2,3,6-trimethylbenzenesulfonyl chloride (4.8 g, 19.3 mmol). After 3 h, the reaction mixture was diluted with ethyl acetate (100 mL) and transferred to a separatory funnel. Aqueous hydrochloric acid (120 mL, 2.5%) was added and the organic layer was separated and washed with 5% sodium bicarbonate and brine and then dried over magnesium sulfate. The organics were removed in vacuo to give 2(R)-(4-methoxy-2,3,6-trimethylbenzenesulfonylamino)-3-methylbutyric acid benzyl ester (8 g) as a brown oil. transferred to a separatory funnel the organic layer was separated washed with 5% sodium bicarbonate and brine dried over magnesium sulfate The organics were removed in vacuo

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

実験手順: 1 N Sodium hydroxide (80 mL) was added to a solution of D-valine benzyl ester trifluoroacetic acid salt (10 g, 31.1 mmol) in methylene chloride (80 mL) and the reaction mixture was stirred until all the starting material was converted to the free amine. The organic phase was collected and washed with brine, dried over magnesium sulfate, and concentrated to give D-valine benzyl ester (5.35 g) as a clear oil. The organic phase was collected washed with brine dried over magnesium sulfate concentrated

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

実験手順: To a solution of D-valine benzyl ester (4 g, 19.3 mmol) and trimethylsilylcyanide (7.2 mL, 57.9 mmol) in acetonitrile (40 mL) was added 4-methoxy-2,3,6-trimethylbenzenesulfonyl chloride (4.8 g, 19.3 mmol). After 3 h, the reaction mixture was diluted with ethyl acetate (100 mL) and transferred to a separatory funnel. Aqueous hydrochloric acid (120 mL, 2.5%) was added and the organic layer was separated and washed with 5% sodium bicarbonate and brine and then dried over magnesium sulfate. The organics were removed in vacuo to give 2(R)-(4-methoxy-2,3,6-trimethylbenzenesulfonylamino)-3-methylbutyric acid benzyl ester (8 g) as a brown oil. transferred to a separatory funnel the organic layer was separated washed with 5% sodium bicarbonate and brine dried over magnesium sulfate The organics were removed in vacuo

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

実験手順: 1 N Sodium hydroxide (80 mL) was added to a solution of D-valine benzyl ester trifluoroacetic acid salt (10 g, 31.1 mmol) in methylene chloride (80 mL) and the reaction mixture was stirred until all the starting material was converted to the free amine. The organic phase was collected and washed with brine, dried over magnesium sulfate, and concentrated to give D-valine benzyl ester (5.35 g) as a clear oil. The organic phase was collected washed with brine dried over magnesium sulfate concentrated

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

実験手順: 1 N Sodium hydroxide (80 mL) was added to a solution of D-valine benzyl ester trifluoroacetic acid salt (10 g, 31.1 mmol) in methylene chloride (80 mL) and the reaction mixture was stirred until all the starting material was converted to the free amine. The organic phase was collected and washed with brine, dried over magnesium sulfate, and concentrated to give D-valine benzyl ester (5.35 g) as a clear oil. The organic phase was collected washed with brine dried over magnesium sulfate concentrated

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

実験手順: 1 N Sodium hydroxide (80 mL) was added to a solution of D-valine benzyl ester trifluoroacetic acid salt (10 g, 31.1 mmol) in methylene chloride (80 mL) and the reaction mixture was stirred until all the starting material was converted to the free amine. The organic phase was collected and washed with brine, dried over magnesium sulfate, and concentrated to give D-valine benzyl ester (5.35 g) as a clear oil. The organic phase was collected washed with brine dried over magnesium sulfate concentrated

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

実験手順: To a solution of D-valine benzyl ester free base (12.92 g, 62 mmol) in dry methylene chloride (120 mL) was added 3,4-(methylenedioxy)phenyl methanol (9.45 g, 62 mmol) and sodium triacetoxyborohydride (18.50 g, 86.8 mmol). After 15 h, the reaction mixture was quenched with saturated aqueous sodium bicarbonate (120 mL) and the aqueous layer was separated and extracted with methylene chloride. The combined methylene chloride layers were washed with brine, dried over magnesium sulfate, and concentrated. The residue was chromatographed (300 g SiO2, 5% ethyl acetate-hexanes) to afford 2(R)-(3,4-methylenedioxy-benzylamino)-3-methylbutyric acid benzyl ester (18 g) as a colorless oil. the reaction mixture was quenched with saturated aqueous sodium bicarbonate (120 mL) the aqueous layer was separated extracted with methylene chloride The combined methylene chloride layers were washed with brine dried over magnesium sulfate concentrated The residue was chromatographed (300 g SiO2, 5% ethyl acetate-hexanes)

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

実験手順: To a solution of D-valine benzyl ester (4 g, 19.3 mmol) and trimethylsilylcyanide (7.2 mL, 57.9 mmol) in acetonitrile (40 mL) was added 4-methoxy-2,3,6-trimethylbenzenesulfonyl chloride (4.8 g, 19.3 mmol). After 3 h, the reaction mixture was diluted with ethyl acetate (100 mL) and transferred to a separatory funnel. Aqueous hydrochloric acid (120 mL, 2.5%) was added and the organic layer was separated and washed with 5% sodium bicarbonate and brine and then dried over magnesium sulfate. The organics were removed in vacuo to give 2(R)-(4-methoxy-2,3,6-trimethylbenzenesulfonylamino)-3-methylbutyric acid benzyl ester (8 g) as a brown oil. transferred to a separatory funnel the organic layer was separated washed with 5% sodium bicarbonate and brine dried over magnesium sulfate The organics were removed in vacuo

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

実験手順: 1 N Sodium hydroxide (80 mL) was added to a solution of D-valine benzyl ester trifluoroacetic acid salt (10 g, 31.1 mmol) in methylene chloride (80 mL) and the reaction mixture was stirred until all the starting material was converted to the free amine. The organic phase was collected and washed with brine, dried over magnesium sulfate, and concentrated to give D-valine benzyl ester (5.35 g) as a clear oil. The organic phase was collected washed with brine dried over magnesium sulfate concentrated

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

実験手順: To a solution of D-valine benzyl ester free base (12.92 g, 62 mmol) in dry methylene chloride (120 mL) was added 3,4-(methylenedioxy)phenyl methanol (9.45 g, 62 mmol) and sodium triacetoxyborohydride (18.50 g, 86.8 mmol). After 15 h, the reaction mixture was quenched with saturated aqueous sodium bicarbonate (120 mL) and the aqueous layer was separated and extracted with methylene chloride. The combined methylene chloride layers were washed with brine, dried over magnesium sulfate, and concentrated. The residue was chromatographed (300 g SiO2, 5% ethyl acetate-hexanes) to afford 2(R)-(3,4-methylenedioxy-benzylamino)-3-methylbutyric acid benzyl ester (18 g) as a colorless oil. the reaction mixture was quenched with saturated aqueous sodium bicarbonate (120 mL) the aqueous layer was separated extracted with methylene chloride The combined methylene chloride layers were washed with brine dried over magnesium sulfate concentrated The residue was chromatographed (300 g SiO2, 5% ethyl acetate-hexanes)