Synthesis
The general procedure for the synthesis of benzyl 2-aminopropionate hydrochloride from L-alanine and benzyl alcohol is as follows:
Example 43: Preparation of HCl-Ala-OBzl
1. 1070 mg (0.012 mol) of L-alanine was added to a mixed solution of 25 mL of benzyl alcohol and 5 g of polyphosphoric acid.
2. The reaction mixture was stirred at 90-95 °C for 4 h. The progress of the reaction was monitored by TLC (unfolding agent: chloroform/methanol, 20:1) until the L-alanine disappeared completely.
3. The reaction mixture was poured into 200 mL of aqueous solution containing 10 mL of concentrated hydrochloric acid and stirred thoroughly.
4. The reaction mixture was extracted with ether (50 mL x 3) to separate the organic and aqueous phases.
5. The organic phase was washed with 2% hydrochloric acid (30 mL x 3).
6. The aqueous phase was combined and the pH was adjusted to 10 with sodium carbonate.
7. The aqueous phase was extracted with 100 mL of ether and the organic phase was dried with anhydrous Na2SO4.
8. The dried organic phase was filtered and hydrogen chloride gas was passed into the filtrate until (S)-benzyl (S)-2-aminopropionate hydrochloride precipitated completely.
9. The precipitate was collected by filtration and dried over anhydrous CaCl2 to give 1500 mg (58% yield) of (S)-benzyl 2-aminopropionate hydrochloride crystals.
10. The melting point of the product was determined to be 140-142°C.
References
[1] ACS Medicinal Chemistry Letters, 2016, vol. 7, # 12, p. 1197 - 1201
[2] Patent: US2005/80015, 2005, A1. Location in patent: Page/Page column 10-11
[3] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 17, p. 6220 - 6229
