Synthesis
General procedure for the synthesis of L-threonine methyl ester hydrochloride from methanol and (2S,3S)-2-amino-3-hydroxybutanoic acid: a mixture of (2S,3S)-2-amino-3-hydroxybutanoic acid (5.4 g, 24.6 mmol) and 6N HCl (60 mL) was refluxed for 5 hours. After completion of the reaction, it was cooled to room temperature and the reaction mixture was extracted with ether (3 x 70 mL) to remove the benzoic acid. The aqueous phase was concentrated to dryness under reduced pressure and the residue was further dried under high vacuum overnight to give crude allo-L-threonine. Methanol (25 mL) was cooled to 0 °C and thionyl chloride (1.80 mL, 25.2 mmol) was added slowly and dropwise. Crude allo-L-threonine was added to the prepared HCl methanol solution and the reaction mixture was heated under reflux conditions for 1 hour. After completion of the reaction, the solvent was removed under vacuum and another batch of HCl methanol solution prepared by the same method was added and the reaction mixture was again heated under reflux for 1 hour. Finally, the solvent was removed in vacuum to give allo-L-threonine methyl ester hydrochloride (4.15 g, 98% overall yield in two steps) as a red solid. The product was identified by 1H NMR (300 MHz, CD3OD): δ 1.27 (d, J = 6.6 Hz, 3H), 4.03 (d, J = 3.3 Hz, 1H), 4.27-4.33 (m, 1H); 13C NMR (75 MHz, CD3OD): δ 17.13,58.17,65.11,167.62; MS ( ESI, positive): m/z 134 [M + H]+.
References
[1] Journal of Organic Chemistry, 2002, vol. 67, # 5, p. 1536 - 1547
[2] Helvetica Chimica Acta, 1957, vol. 40, p. 1531,1544
[3] Journal of Organic Chemistry, 1997, vol. 62, # 21, p. 7364 - 7375
[4] Journal of Organic Chemistry, 2003, vol. 68, # 26, p. 10046 - 10057
[5] Journal of the American Chemical Society, 2007, vol. 129, # 18, p. 6017 - 6021
