ethyl (2S)-2-methylsulfonyloxypropanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of bis(2-chloroethyl)amine hydrochloride (0.392 g; 2.1 mmol) in 5N aqueous sodium hydroxide (3 mL) is extracted with ether (2×10 mL) and the combined extracts are washed with a minimum amount of water and saturated brine. The ethereal solution is dried quickly over magnesium sulfate and filtered. Tetrahydrofuran (2 mL) is added to the filtrate, and ether is carefully removed under reduced pressure on a rotavapor unit without heating. The residue is mixed with a solution of ethyl (S)-2-[(methylsulfonyl)oxy]-propionate (0.5 g; 2 mmol) in tetrahydrofuran (1 mL). After stirring the reaction mixture for 24 hrs at room temperature, there is no visible precipitate. The volatiles are removed under reduced pressure and the remaining viscous oil is dissolved in ether (8 mL), and the slightly turbid solution is filtered after 60 minutes. The filtrate is treated dropwise with n-heptane to induce crystallization; the final ratio of n-heptane/ether is 1:3. The crystalline salt is collected by filtration and washed quickly with a small portion of ether. There is obtained 0.653 g (yield 83.3%) of N,N-bis(2-chloroethyl)-(R)-alanine ethyl ester, trifluoromethanesulfonate; mp 73-74.5° C.; 1H NMR (300 MHz, CDCl3) δ 1.35 (t, J=7.1 Hz, 3H), 1.76 (d, J=7.2 Hz, 3H), 3.87 (m, 2H), 4.00 (m, 2H), 4.35 (q, J=7.1 Hz, 2H), 4.57 (q, J=7.2 Hz, 1H), 9.02 (b, 1H). is extracted with ether (2×10 mL) the combined extracts are washed with a minimum amount of water and saturated brine The ethereal solution is dried quickly over magnesium sulfate filtered Tetrahydrofuran (2 mL) is added to the filtrate, and ether is carefully removed under reduced pressure on a rotavapor unit without heating The volatiles are removed under reduced pressure the remaining viscous oil is dissolved in ether (8 mL) the slightly turbid solution is filtered after 60 minutes The filtrate is treated dropwise with n-heptane crystallization The crystalline salt is collected by filtration washed quickly with a small portion of ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An equal molar solution of (S)-ethyl lactate and triethylamine in dry methylene was treated with an equal molar amount of methane sulfonylchloride at 5°-10° C. After the addition was complete, the mixture was filtered to remove triethylamine hydrochloride. The filtrate was then washed with water, dried over MgSO4, and concentrated to give a high yield of ethyl-(S)-2[(methylsulfonyl)oxy]propionate. After the addition the mixture was filtered to remove triethylamine hydrochloride The filtrate was then washed with water dried over MgSO4 concentrated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-ethyl 2-(methylsulfonyloxy)propanoate (28.4 g, 0.1 mol) in N,N′-dimethylformamide (400 mL) was added dibenzyl malonate (23.5 g, 0.12 mol) and cesium fluoride (15.2 g, 0.1 mol). The mixture was heated at 50° C. for 2 days. After cooled to room temperature, the mixture was poured into water and then extracted with ethyl acetate. The organic phases were combined, washed with brine, water and dried over anhydrous sodium sulfate, and then concentrated to afford the crude product (S)-1,1-dibenzyl 2-ethyl propane-1,1,2-tricarboxylate, which was purified by silica gel chromatography (23 g, yield 60%). After cooled to room temperature extracted with ethyl acetate washed with brine, water dried over anhydrous sodium sulfate concentrated

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (L)-ethyl lactate (124 g, 1.05 mol) and triethyl amine (126 g, 1.25 mol) in toluene at 10-15° C. was added methanesulfonyl chloride (124 g, 1.08 mol) dropwise for about 2 hours. The mixture was allowed to warm to about 20° C. and the solid was filtered off. The solution was washed with water and dried, concentrated to afford the product (S)-ethyl 2-(methylsulfonyloxy)propanoate (199 g, yield 96.7%). the solid was filtered off The solution was washed with water dried concentrated