Dimethyl Sulfoxide → (S)-4-Benzyloxy-2-[2-(3,4-dichloro-phenylamino)-propylamino]-butyric acid methyl ester

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Reaction Steps

To a solution of 0.73 ml (8.36 mmol) of oxalyl chloride in 21 ml CH2Cl2 at −50 to −60° C. was added a solution of 1.24 ml (17.45 mmol) dimethylsulfoxide in 5 ml of CH2Cl2 within 10 min. The solution was stirred for 5 min and a solution of 1.600 (7.27 mmol) 2-(3,4-dichloro-phenylamino)-propan-1-ol in 21 ml of CH2Cl2 was added within 10 min. The mixture was stirred for 15 min and 5.07 ml (36.35 mmol) of triethylamine were added within 20 min. The suspension was stirred for 75 min and slowly warmed to 0° C. (complete oxidation followed by TLC, SiO2, EtOAc:n-heptane 1:1). 1.88 g (7.27 mmol) of (S)-2-amino-4-benzyloxy-butyric acid methyl ester hydrochloride (intermediate 5) was added and 0.9 ml of acetic to adjust the pH to 5 followed by 1.75 g (8.00 mmol) of sodium triacetoxyborohydride. After 5 min at 0° C. and 1.5 h at RT, the reaction was poured on a solution of sat. aq. NaHCO3 solution, followed by extraction with EtOAc (3 times). The organic phases were washed with a solution of 10% aq. NaCl solution. The combined organic phases were dried over Na2SO4 and the solvent was removed under vacuum to give 3.13 g (quantitative) of the title compound as a 71:29 mixture of the (R) and (S) diastereomers. Yellow oil, MS: 425.2 (MH+, 2Cl).

Provenance & Evidence