C(N([CH2:6][CH3:7])CC)C.[N:8]1([C:13]2[CH2:14][N:15]([C:18]([O:20][CH3:21])=[O:19])[CH2:16][CH:17]=2)[CH2:12][CH2:11][CH2:10][CH2:9]1.C([CH:24]([C:28](Cl)=[O:29])[C:25](Cl)=[O:26])C.CC[O:33]CC>CN(C)C1C=CN=CC=1>[C:28]([CH2:24][C:25]([C:17]1[CH2:16][N:15]([C:18]([O:20][CH3:21])=[O:19])[CH2:14][C:13]=1[N:8]1[CH2:9][CH2:10][CH2:11][CH2:12]1)=[O:26])([O:29][CH2:6][CH3:7])=[O:33]Pyrrolidine (25 ml) is slowly added dropwise to a stirred suspension of 28.63 g of N-methoxycarbonyl-3-oxo-tetrahydropyrrole [prepared according to J Med Chem 5, 752 (1962)] and 29.5 g of anhydrous potassium carbonate in 200 ml ether and 100 ml toluene at 0°-5° under a nitrogen atmosphere. After 3 hours the suspension is filtered and the filtrate evaporated under reduced pressure to yield 3-pyrrolidino-N-methoxycarbonyl-2,5-dihydropyrrole as an oil. NMR (CDCl3): 4.12 (s), 4.01 (m), 3.63 (s), 3.00 (m), and 1.85 (m). Triethylamine (28 ml) and 2,4 g of 4-dimethylaminopyridine are added to a solution of 39.3 g (0.2 moles) of 3-pyrrolidino-N-methoxycarbonyl-2,5-dihydropyrrole in 850 ml of dry ether. The reaction mixture is cooled in an ice bath. A solution of 25.6 ml of ethyl malonyl chloride in 850 ml ether is added dropwise keeping the internal temperature below 5°. After 1 hour at 5° and 2 hours at room temperature, the suspension is filtered, the ether solution is washed with 10% ice cold citric acid and saturated NaHCO3 solution. The organic layer is dried over MgSO4, filtered and evaporated to yield 3-carboethoxyacetyl-4-pyrrolidino-N-methoxycarbonyl-2,5 dihydropyrrole as an oil; NMR (CDCl3) 4.44 (s), 4.37 (s), 4.17 (q) 3,73 (s), 3,42 (m), 3.32 (s), 1.90 (m) and 1.26 (t).
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