Chemical Properties
off-white powder
Uses
Boc-D-3-pyridylalanine, is an alanine derivative, used in various chemical synthesis and peptide chemistry.
Synthesis
To a suspension of methanol (3.0 mL) containing 3-(3-pyridyl)-D-alanine nickel(II) complex (100.0 mg, 0.130 mmol) was added 1N hydrochloric acid (0.65 mL, 0.648 mmol). The mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure and the residue was subjected to liquid-liquid separation with dichloromethane (10 mL) and water (10 mL). The aqueous layer was separated and the solvent was removed by evaporation. The resulting solid was dissolved in 8% ammonia (5 mL) and the solution was purified by passing through a cation exchange resin column (SK-1B, 40 mL, eluent: water followed by 4% ammonia) to afford 3-(3-pyridinyl)-D-alanine (17.7 mg, Yield: 81.9%, 97.3% ee) as a white solid.The conditions for HPLC analysis were as follows: column: CROWNPAK CR( +) (5 μm, 150×4.0 mm I.D.); eluent: aqueous perchloric acid (pH 1.0); flow rate: 0.4 mL/min; temperature: 30 ℃; detector: UV 254 nm; retention time (min) and enantiomeric excess ratio as shown in Table 9. The organic layer was washed with 2% ammonia (10 mL, twice), water (10 mL, twice) and saturated brine (10 mL, twice), dried over sodium sulfate and evaporated to remove the solvent to obtain the chiral auxiliary (S-isomer) (63.8 mg, chemical purity: 98.6%, yield: 86.9%). 3-(3-Pyridyl)-D-alanine (16.3 mg, 0.098 mmol) was dissolved in water (1 mL) and acetone (0.5 mL), and acetone (0.25 mL) solution of di-tert-butyl dicarbonate (Boc)2O (34.3 mg, 0.157 mmol) and acetone ( 0.25 mL) solution of triethylamine (15.9 mg, 0.157 mmol) were added. 0.25mL) solution. The mixture was stirred at room temperature for 3.5 hours. After the reaction mixture was concentrated under reduced pressure to a volume ≤ 1 mL, 2-butanol (10 mL) was added. The pH of the aqueous layer was adjusted to 2-3 with 1N hydrochloric acid and the aqueous layer was extracted with 2-butanol (10 mL, 3 times). The organic layer was washed with saturated brine (10 mL, twice), dried over magnesium sulfate and evaporated to remove the solvent to give Boc-3-(3-pyridinyl)-D-alanine (20.5 mg, Yield: 78.5%, Chemical purity: 97.1%) as a colorless solid.
References
[1] Journal of Medicinal Chemistry, 1986, vol. 29, # 10, p. 1846 - 1851
[2] Patent: US2016/102045, 2016, A1. Location in patent: Paragraph 0325-0332
[3] Patent: KR2015/133268, 2015, A. Location in patent: Paragraph 0535; 0537; 0549
[4] Journal of Medicinal Chemistry, 2006, vol. 49, # 26, p. 7592 - 7595
[5] Patent: WO2018/167468, 2018, A1. Location in patent: Page/Page column 71
