L-Alanine, phenylmethyl ester, 4-methylbenzenesulfonate (1:1)

Yellowish Oil

Into a 300 mL separable flask equipped with a thermometer, stirring apparatus and Dean Stark apparatus was charged 5.00 g (56.12 mmol) of L-alanine, 41.03 g (379.42 mmol) of benzyl alcohol and 12.81 g (67. 34 mmol) of p-toluenesulfonic acid, and mixed, then, the pressure was reduced from 101.3 kPa to 2.0 kPa. The reaction solution was heated, then, water started to be distilled at the inner temperature around 50°C, and the mixture was heated up to 62°C over a period of 2 hours. Under the same pressure and the same temperature, the mixture was stirred for 3.5 hours. The reaction solution was cooled down to 50°C, and 111.66 g of tert-butyl methyl ether was dropped over a period of 30 minutes, then, about 0.005 g (0.01 mmol) of p-toluenesulfonate of L-alanine benzyl ester was added. The mixture was stirred at 50°C for 30 minutes, then, 55.83 g of tert-butyl methyl ether was dropped over a period of 1 hour. The mixture was stirred at 50°C for 1 hour, then, cooled from 50°C to 0°C over a period of 5 hours, and the mixture was stirred at 0°C overnight. The mixture was subjected to a filtration treatment, and the resultant crystal was washed three times with 15.00 g of tert-butyl methyl ether of 0°C. After drying, 18.26 g of p-toluenesulfonate of L-alanine benzyl ester was obtained. The yield against L-alanine was 98.6percent. The optical purity of the p-toluenesulfonate of L-alanine benzyl ester was 99.9percent e.e. or more.General procedure: The esterifications were carried out on L amino acids withthe exception of phenylglycine, the D enantiomer of whichwas used. A mixture of amino acid (0.05 mol), p-toluenesulfonicacid (0.06 mol), benzyl alcohol (0.25 mol) andcyclohexane (30 mL) was refluxed for 4 h using a Dean-Stark apparatus to separate water that was azeotroped outas it formed. The reaction mixture was cooled to roomtemperature and ethyl acetate (80 mL) was added. Afterstirring for 1 h, the precipitate was collected by filtrationand dried to give the corresponding benzyl ester p-toluenesulfonateas a white solid. According to this procedure, the amino acids 1–6 were converted into the correspondingbenzyl ester p-toluenesulfonates 1a–6a. The benzylationof 7 was accomplished in the same manner but in thepresence of more p-toluenesulfonic acid (0.11 mol) to givethe di-p-toluenesulfonate 7a as a white solid. The p-toluenesulfonate8a separated at the end of the reaction as anoil; instead of adding ethyl acetate, the supernatant wasremoved, the oily phase was washed with cyclohexane andthen poured into dichloromethane/aqueous Na2CO3. Afterremoving the water layer and evaporating dichloromethane, the residue was treated with hydrochloric methanol to give the corresponding hydrochloride as a white solid. Thebenzylation of 9 was prolonged over night and, at the endof the reaction, 9a separated as an oil, which was pouredinto dichloromethane/water. After removing the organiclayer, the water phase was made alkaline with NaHCO3 andextracted with ethyl acetate. The organic extract was concentratedto a small volume and a slight excess of p-toluenesulfonicacid was added to precipitate 9a as a white crystallinesolid.To a solution of L-alanine (Scheme 2, compound 1-D) (1151.2 mg, 12.9 mmol, 1.00 eq) in 51 mL of toluene, were added (i) 23 mL of BnOH; and (ii) 2457.6 g of APTS.H

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Molecular Weight:351.4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:5
Exact Mass:351.11404394
Monoisotopic Mass:351.11404394
Topological Polar Surface Area:115
Heavy Atom Count:24
Complexity:371
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes