Methyl Acetate → 3-(2-Methyl-propane-2-sulfinylamino)-3-phenyl-propionic acid methyl ester

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Reaction Conditions

Reaction Steps

Under anhydrous conditions a solution of i-Pr2NH (2.2 eq) in 60 mL THF is cooled to 0° C. (J. Org. Chem. 2003, 68, 9948-9957). n-BuLi (2.1 eq, 1.6 M solution in hexane) is added via syringe and the solution is stirred for 30 min. The solution is then cooled to −78° C. A solution of acetic acid methyl ester (2 eq) in 1 mL of THF is added via syringe and the reaction solution is stirred for 30 min. To this solution is added ClTi(Oi-Pr)3 (4.2 eq) in 20 mL THF and the solution is stirred for 30 min. A solution of the tert.-butane-sulfinic acid 1-phenyl-methylidene amide (5.4 mmol, 1 eq) in 5 mL THF is slowly added via syringe and the solution is stirred for 3 h at −78° C. Upon reaction completion as determined by TLC, a saturated aqueous solution of NH4Cl (5 mL) is added and the suspension is warmed to room temperature. The mixture is diluted with H2O and vigorously stirred to dissolve the precipitate. The mixture is then decanted into a separatory funnel, and the remaining solid is diluted with equal parts of H2O and ethyl acetate and vigorously stirred for 15 min. The mixture is then added to the separatory funnel and the organic layer is collected. The aqueous layer is then extracted 3× with ethyl acetate. The combined organic layers are washed with brine, dried with Na2SO4, and concentrated in vacuo. 3-(2-Methyl-propane-2-sulfinylamino)-3-phenyl-propionic acid methyl ester is obtained as a clear colourless solid (102% yield); ES-MS (MH+)=284.1; 1H-NMR (DMSO-d6, 400 MHz): δ [ppm] 7.35-7.23 (m, 5H), 5.59 (d, 1H, 6.1 Hz), 4.63 (m, 1H), 3.54 (s, 3H), 3.04-2.99 (m, 1H), 2.80-2.74 (m, 1H), 1.06 (s, 9H).

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