تفاعل #73371

معادلة التفاعل

formamidine acetate

NaH

ethoxycarbonylamino-acetic acid ethyl ester

toluene

sodium ethoxide

but-2-enoic acid ethyl ester

→

title compound

(±)-5-Methyl-4-oxo-3,4,5,7-tetrahydro-pyrrolo[3,4-d]pyrimidine-6-carboxylic acid tert-butyl ester

المذيبات

Ethanol

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONis added at 0° C
2. 2
   workup.WAITThe reaction is left
3. 3
   workup.STIRRINGstirred for further 2 h
4. 4
   أخرىthe reaction is then evaporated
5. 5
   workup.DISSOLUTIONThe crude 1-tert-butyl 3-ethyl 2-methyl-4-oxopyrrolidine-1,3-dicarboxylate is dissolved in EtOH (1500 mL)
6. 6
   workup.WAITThe reaction is left
7. 7
   workup.STIRRINGstirring at 90° C. for 8 h
8. 8
   أخرىThe solvent is then removed and to the crude material a saturated solution of NH4Cl (200 mL)
9. 9
   workup.ADDITIONis added
10. 10
    استخلاصThe water layer is extracted two times with DCM
11. 11
    أخرىThe organics are dried
12. 12
    أخرىevaporate
13. 13
    أخرىThe crude product is separated by FCC (DCM/MeOH 100:0 to 90:10)

الإجراء التجريبي

To a suspension of NaH (9.72 g, 243 mmol, 60% in mineral oil) in toluene (100 mL), ethoxycarbonylamino-acetic acid ethyl ester (38 g, 187 mmol) is added at 0° C. The reaction is left stirring for 5 h at the same temperature. At that point but-2-enoic acid ethyl ester (25.6 g, 224 mmol) is added and the reaction allowed to warm up to rt and stirred for further 2 h. Ethanol (30 mL) is added and the reaction is then evaporated. The crude 1-tert-butyl 3-ethyl 2-methyl-4-oxopyrrolidine-1,3-dicarboxylate is dissolved in EtOH (1500 mL), then formamidine acetate (343 g, 1189 mmol) is added followed by sodium ethoxide (47.2 g, 694 mmol). The reaction is left stirring at 90° C. for 8 h. The solvent is then removed and to the crude material a saturated solution of NH4Cl (200 mL) is added followed by DCM (1 L). The water layer is extracted two times with DCM. The organics are dried and evaporate. The crude product is separated by FCC (DCM/MeOH 100:0 to 90:10) to give the title compound. MS (ESI) m/z 252.2 (M+1).

المصدر