(2S)-2-morpholin-4-ylpropanoic acid

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

Procedure: To a solution of N-{2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl}-N-methylamine (45 mg, 0.15 mmol) in pyridine (1 ml) were added (S)-2-(morpholin-4-yl)propionic acid obtained in Reference Example 3 (110 mg, 0.69 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (106 mg, 0.55 mmol) at room temperature, and the mixture was stirred for 14 hr. To the reaction mixture were added chloroform and water, and the organic layer was separated. The organic layer was dried over sodium sulfate. Sodium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. Then, the residue was dissolved in a mixed solvent of tetrahydrofuran (1 ml) and methanol (1 ml). To the solution was added 2 N aqueous sodium hydroxide solution (0.35 ml) at room temperature, and the mixture was stirred for 20 min. To the reaction mixture were added chloroform and water, and the organic layer was separated. The organic layer was dried over sodium sulfate. Sodium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by thin layer silica gel chromatography to give the title compound (52 mg, yield 78%). the organic layer was separated The organic layer was dried over sodium sulfate Sodium sulfate was removed by filtration the filtrate was concentrated under reduced pressure Then, the residue was dissolved in a mixed solvent of tetrahydrofuran (1 ml) and methanol (1 ml) To the solution was added 2 N aqueous sodium hydroxide solution (0.35 ml) at room temperature the mixture was stirred for 20 min To the reaction mixture were added chloroform and water the organic layer was separated The organic layer was dried over sodium sulfate Sodium sulfate was removed by filtration the filtrate was concentrated under reduced pressure The residue was purified by thin layer silica gel chromatography

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

Procedure: Under an argon atmosphere, to a solution of benzyl (S)-2-(morpholin-4-yl)propionate (43 g, 172 mmol) in methanol (430 ml) was added 20% palladium hydroxide-carbon (4.3 g) at room temperature, and the mixture was stirred for 3 hr under a hydrogen atmosphere at normal pressure. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure to give the title compound (25.4 g, 93%). The reaction mixture was filtered through celite the filtrate was concentrated under reduced pressure