Chemical Properties
white to light yellow crystal powde
Uses
Boc-Phe(4-F)-OH, is an amino acid building block used in peptide synthesis. With a growing peptide drug market the fast, reliable synthesis of peptides is of great importance.
reaction suitability
reaction type: Boc solid-phase peptide synthesis
Synthesis
General procedure for the synthesis of Boc-L-4-fluorophenylalanine from di-tert-butyl dicarbonate and (S)-2-amino-3-(4-fluorophenyl)propionic acid: (S)-2-amino-3-(4-fluorophenyl)propionic acid (1.97 g, 10 mmol) was dissolved in a mixture of dioxane (20 mL), water (20 mL), and 1 M NaOH (10 mL), stirred and cooled in an ice water bath. Di-tert-butyl dicarbonate (2.4 g, 11 mmol) was added slowly and the reaction mixture was continued to be stirred for 6 hours at room temperature. Upon completion of the reaction, the solution was concentrated under reduced pressure to about 15-20 mL and then cooled in an ice water bath. The concentrate was covered with ethyl acetate (~30 mL) and acidified to pH 2-3 with the addition of dilute KHSO4 solution. the aqueous phase was separated and extracted three times with ethyl acetate. The organic phases were combined, dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a waxy solid product. Yield: 2.115 g (7.25 mmol, 72.5% yield). The product was characterized by 1H NMR and MALDI-TOF mass spectrometry: 1H NMR (DMSO-d6, 400 MHz, ppm): δ 12.60 (s, 1H, COOH), 7.29-7.25 and 7.11-7.07 (m, 4H, aromatic protons), 4.10-3.00 (m, 1H, CH), 3.03-2.77 ( m, 2H, CH2), 1.33 (s, 9H, Boc). MALDI-TOF (Substrate: α-cyano-4-hydroxycinnamic acid (CHCA)): m/z = [M + H]+ 284.12 (calculated), 284.29 (observed), [M + Na]+ 306.11 (calculated), 306.25 (observed).
References
[1] Chemical Communications, 2014, vol. 50, # 76, p. 11154 - 11157
[2] Patent: WO2017/42805, 2017, A1. Location in patent: Page/Page column 24; 25
[3] Journal of Medicinal Chemistry, 1994, vol. 37, # 13, p. 2090 - 2099
[4] Bioorganic and Medicinal Chemistry, 1996, vol. 4, # 10, p. 1733 - 1745
