L-Valine benzyl ester 4-toluenesulfonate

72-18-4

104-15-4

100-51-6

16652-76-9

GENERAL STEPS: The esterification reaction was carried out on L-amino acids, except phenylglycine, where the D-enantiomer was used. A mixture of L-valine (0.05 mol), 4-methylbenzenesulfonic acid (0.06 mol), benzyl alcohol (0.25 mol), and cyclohexane (30 mL) was refluxed for 4 hours using a Dean-Stark apparatus to separate the water with which it formed an azeotrope. After cooling the reaction mixture to room temperature, ethyl acetate (80 mL) was added. After stirring for 1 hour, the precipitate was collected by filtration and dried to give L-valyl benzyl ester p-toluenesulfonate as a white solid. Following this method, amino acids 1-6 were converted to the corresponding benzyl p-toluenesulfonate 1a-6a. benzylation of compound 7 was carried out in the same manner but in the presence of more 4-methylbenzenesulfonic acid (0.11 mol) to give di-p-toluenesulfonate 7a as a white solid. The p-toluenesulfonate 8a separated as an oil at the end of the reaction; instead of adding ethyl acetate, the supernatant was removed, the oil phase was washed with cyclohexane, and poured into an aqueous solution of dichloromethane/Na2CO3. After separation of the aqueous layer, the dichloromethane was evaporated and the residue was treated with methanol hydrochloride to give the corresponding hydrochloride salt as a white solid. The benzylation of compound 9 was prolonged overnight and at the end of the reaction, 9a separated as an oil, which was poured into dichloromethane/water. After removal of the organic layer, the aqueous phase was alkalized with NaHCO3 and extracted with ethyl acetate. The organic extract was concentrated to a small volume and a slight excess of 4-methylbenzenesulfonic acid was added to precipitate 9a as a white crystalline solid.