تفاعل #47334

معادلة التفاعل

(S)-2-[4-(3-chloro-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester

lithium hydroxide monohydrate

→

(S)-2-[4-(3-chloro-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid

المردود 90.0%

المذيبات

tetrahydrofuran

water

water

ظروف التفاعل

المعالجة

1. 1
   استخلاصextracted with diethyl ether (1×75 mL)
2. 2
   استخلاصextracted with ethyl acetate (3×50 mL)
3. 3
   تجفيفThe combined organics were dried over magnesium sulfate
4. 4
   ترشيحfiltered
5. 5
   غسيلrinsed with ethyl acetate
6. 6
   تركيزconcentrated in vacuo

الإجراء التجريبي

A mixture of (S)-2-[4-(3-chloro-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester (0.87 g, 2.46 mmol) in tetrahydrofuran (15 mL) and water (5 mL) was treated with lithium hydroxide monohydrate (0.12 g, 2.85 mmol). The reaction was stirred at 25° C. for 2.5 h. At this time, the reaction was diluted with water (75 mL) and extracted with diethyl ether (1×75 mL). The aqueous layer was acidified with a 2N aqueous hydrochloric acid solution and then extracted with ethyl acetate (3×50 mL). The combined organics were dried over magnesium sulfate, filtered, rinsed with ethyl acetate and concentrated in vacuo to afford (S)-2-[4-(3-chloro-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (0.75 g, 90%) as a light orange solid: HR-ES-MS m/z calculated for C16H17NO4FCl [M+H]+ 342.0903, observed 342.0904; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.87 (d, J=6.5 Hz, 3H), 0.93 (d, J=6.5 Hz, 3H), 1.35-1.56 (m, 1H), 1.56-1.70 (m, 1H), 1.72-1.86 (m, 1H), 4.19 (d, J=18.2 Hz, 1H), 4.29 (d, J=18.2 Hz, 1H), 4.63 (dd, J=11.5, 4.3 Hz, 1H), 5.05 (s, 1H), 7.33 (td, J=8.3, 1.4 Hz, 1H), 7.49-7.55 (m, 1H), 7.57 (ddd, J=8.3, 6.8, 1.4 Hz, 1H), 12.92 (br. s., 1H).

المصدر