تفاعل #2846

معادلة التفاعل

(2-oxo-pyrrolidin-3-(S)-yl)-carbamic acid tert-butyl ester

4-bromomethyl-thiophene-2-carbonitrile

sodium hydride

→

title compound

المردود 86.3%

[1-(5-Cyanothiophene-3-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-carbamic acid tert-butyl ester

المردود 86.3%

المذيبات

THF DMF

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONAfter addition
2. 2
   درجة الحرارةto warm to ambient temperatures
3. 3
   أخرىthe solution is quenched by the addition of sat. NH4Cl
4. 4
   workup.ADDITIONThe solution is diluted with H2O and EtOAc
5. 5
   أخرىThe layers are separated
6. 6
   غسيلThe organic layer is washed with H2O and sat. NaCl
7. 7
   تجفيفThe organic layer is dried over MgSO4
8. 8
   ترشيحfiltered
9. 9
   تركيزconcentrated
10. 10
    أخرىThe crude product is purified by column chromatography
11. 11
    غسيلeluting with gradient of 20% EtOAc/CH2 Cl2 to 30% EtOAc/CH2Cl2

الإجراء التجريبي

To a solution of (2-oxo-pyrrolidin-3-(S)-yl)-carbamic acid tert-butyl ester (3.2 g, 16 mmol), prepared as described in EXAMPLE 1, Part A in 80 mL of THF:DMF (10:1) at 0° C. is added 4-bromomethyl-thiophene-2-carbonitrile (3.23 g, 16 mmol) and sodium hydride (60% dispersion in oil, 0.67 g, 16.8 mmol). After addition, the solution was allowed to warm to ambient temperatures. After 2 h, the solution is quenched by the addition of sat. NH4Cl. The solution is diluted with H2O and EtOAc. The layers are separated. The organic layer is washed with H2O and sat. NaCl. The organic layer is dried over MgSO4, filtered and concentrated. The crude product is purified by column chromatography eluting with gradient of 20% EtOAc/CH2 Cl2 to 30% EtOAc/CH2Cl2 to afford the title compound (4.0 g, 13.8 mmol) as a white solid.

المصدر