تفاعل #47688

معادلة التفاعل

(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide

hydrochloric acid

→

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

المردود 86.0%

المذيبات

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   أخرىAt this time the mixture was partitioned between ethyl acetate and water
2. 2
   أخرىThe layers were separated
3. 3
   استخلاصthe aqueous layer was extracted with ethyl acetate
4. 4
   غسيلThe combined organic layers were washed with brine
5. 5
   تجفيفdried over sodium sulfate
6. 6
   ترشيحThe mixture was filtered
7. 7
   تركيزconcentrated in vacuo
8. 8
   أخرىthe residue was purified by ISCO flash chromatography (RediSep silica column 12 g, 30% to 80% (10% methanol/dichloromethane)hexanes) which

الإجراء التجريبي

A solution of (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (360 mg, 0.7 mmol) in tetrahydrofuran (15 mL) was treated with 2N aqueous hydrochloric acid (7.5 mL) and stirred at room temperature for 2.5 h. At this time the mixture was partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. The mixture was filtered and concentrated in vacuo and the residue was purified by ISCO flash chromatography (RediSep silica column 12 g, 30% to 80% (10% methanol/dichloromethane)hexanes) which afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide (285 mg, 86%) as a white fluffy solid: HR-ES-MS (m/z) calculated for C23H29ClN4O5 [M+H]+ 477.1899, observed 477.1897. 1H NMR showed mixture of diastereomers (400 MHz, DMSO-d6) δ ppm 0.77-0.96 (m, 6H), 1.04-1.93 (m, 5H), 3.23-3.33 (m, 2H), 3.77 (br. s., 1H), 3.82-3.91 (m, 1H), 4.04-4.14 (m, 1H), 4.11-4.29 (m, 1H), 4.58, 4.63 (2×d, J=18.7 Hz, 1H), 4.71 (br. s., 1H), 4.79, 4.81 (2×s, 1H), 4.86-4.97 (m, 2H), 6.42 (br. s., 1H), 7.37 (t, J=7.7 Hz, 1H), 7.46 (t, J=7.5 Hz, 1H), 7.49-7.56 (m, 2H), 7.65 (d, J=7.9 Hz, 1H), 10.77, 10.79 (2×s, 1H)

المصدر