Reacción #47475

Ecuación de reacción

Hydrochloric acid

(R)-4-(3-{(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-pyrazol-1-ylmethyl)-2,2-dimethyl-oxazolidin-3-carboxylic acid t-butyl ester

→

(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2-amino-3-hydroxy-propyl)-1H-pyrazol-3-yl]-amide

Rendimiento 47.0%

Disolventes

diethyl ether

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroprecipitates out of solution
2. 2
   OtroThe diethyl ether was decanted off
3. 3
   Lavadothe solid washed with three portions of diethyl ether
4. 4
   OtroThe crude product was purified via supercritical fluid chromatography on a DAICEL AD column, 25% methanol, 70 mL/min

Procedimiento

Hydrochloric acid gas was bubbled into a stirred solution of (R)-4-(3-{(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-pyrazol-1-ylmethyl)-2,2-dimethyl-oxazolidin-3-carboxylic acid t-butyl ester (1.00 g, 16.63 mmol) in diethyl ether (20 mL) for 30 seconds. The reaction mixture was then stirred at room temperature for 30 min during which a white solid precipitates out of solution. The diethyl ether was decanted off and the solid washed with three portions of diethyl ether. The crude product was purified via supercritical fluid chromatography on a DAICEL AD column, 25% methanol, 70 mL/min to afford (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2-amino-3-hydroxy-propyl)-1H-pyrazol-3-yl]-amide (362 mg, 47%) as a white solid: LR-ES-MS m/z calculated for C22H28ClN5O4 [M]+ 461, observed 462 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H), 1.34-1.85 (m, 5H), 3.00 (br. s., 1H), 3.22 (br. s., 2H), 3.80 (dd, J=13.4, 6.9 Hz, 1H), 4.02 (dd, J=13.4, 5.0 Hz, 1H), 4.21 (d, J=18.4 Hz, 1H), 4.61 (d, J=18.4 Hz, 1H), 4.65-4.75 (m, 1H), 4.79 (s, 1H), 4.89 (dd, J=9.8, 4.1 Hz, 1H) H), 6.42 (s, 1H), 7.31-7.42 (m, 1H), 7.42-7.55 (m, 2H), 7.57 (br. s., 1H), 7.65 (d, J=7.2 Hz, 1H), 10.79 (br. s., 1H).

Fuente