p-Toluenesulfonic acid → (2S,4R)-2-t-butoxycarbonylamino-4-ethoxy-pentanoic acid

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Reaction Steps

To a cooled solution of (S)-4-((R)-2-hydroxy-propyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester (730 mg, 2.81 mmol) in dry tetrahydrofuran (15 mL) was added sodium hydride at 0° C. (60% in mineral oil, 248 mg). The suspension was warmed to room temperature and ethyl iodide (1.2 mL) was added. The mixture was stirred overnight and extracted with diethyl ether and saturated sodium chloride solution. The organic layer was washed with saturated sodium chloride solution and dried over sodium sulfate. After the evaporation of solvents, an oily material was obtained (660 mg). This oily material was dissolved in a mixture of tetrahydrofuran (1 mL) and methanol (10 mL). To this solution was added p-toluene sulfonic acid (22 mg). The mixture was stirred at room temperature overnight. Solvents were evaporated and the residue was extracted with ethyl acetate and sodium bicarbonate solution. After the evaporation of solvents, the resulting oily compound (532 mg) was dissolved in a mixture of acetonitrile (11 mL) and phosphate buffer (8 mL, pH=7). Then 1-oxyl-2,2,6,6-tetramethylpiperidine (24 mg) and sodium chlorite (495 mg) in water (2.5 mL) were added. The solution was warmed to 35° C. and catalytic amount of diluted bleach (1 mL of 5.25% sodium hypochlorite solution diluted to 20 mL in water, 1 mL of the diluted solution was used) was added in 5 portions. The mixture was stirred for 2 h. Then second portion of sodium chlorite (495 mg) in water (2.5 mL) was added. The mixture was stirred at room temperature overnight. The mixture was cooled to 0° C. and adjusted to pH=9 with dilute sodium hydroxide solution. Sodium sulfite solution (2.7 g) in water (30 mL) was added and the mixture was stirred for 20 min. The resulting solution was extracted with methyl t-butyl ether. The organic layer was discarded and the aqueous layer was acidified with 1N aqueous hydrochloric acid to pH value about 2.0. The mixture was extracted with methyl t-butyl ether three times and dried over sodium sulfate. Solvents were evaporated to afford (2S,4R)-2-t-butoxycarbonylamino-4-ethoxy-pentanoic acid (279 mg) as a thick oil: LR-ES-MS m/z calculated for C12H23NO5 [M] 261, observed 260 [M−H]; 1H NMR (300 MHz, CDCl3) δ ppm 1.18 (t, 7.2 Hz, 3H), 1.22 (d, J=6.3 Hz, 3H), 1.46 (s, 9H), 1.88-2.16 (m, 2H), 3.26-3.43 (m, 1H), 3.55-3.72 (m, 2H), 4.27-4.39 (m, 1H), 5.59 (br. s., 1H), 10.51 (br. s., 1H).

Provenance & Evidence