Sulfuric Acid → HCID 69074709, compound

Participants

Reaction Steps

2(S)(3-carboxy-2-oxo-1-pyrrolidinyl)-4-methyl pentanoic acid methyl ester was prepared according to the method of R. M. Freidinger, J.Org.Chem., 1985, 50 (19):3631-3633. A solution of isopropylidene cyclopropane-1,1-dicarboxylate (5.0 g, 29.30 mmol), leucine methyl ester hydrochloride (5.31 g, 29.3 mmol), and triethylamine (2.97 g, 29.3 mmol) in degassed DMF (50 mL) was heated at 65° C. for 1 hour. The solution was cooled to ambient temperature and poured into a mixture of 10% aqueous sulfuric acid (H2SO4) (100 mL) and ethyl acetate (100 mL). The organic layer was separated. After drying with Na2SO4, the solvent was removed in vacuo to yield 7.55 g of a brown oil. To the crude oil (7.55 g) in degassed DMF (50 mL) were added 3-(dimethylaminomethyl)indole (gramine) methiodide (13.2 g, 42.94 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (5.16 g, 33.90 mmol). The mixture was heated at 85° C. for 18 hours and cooled to ambient temperature. The mixture was poured into ethyl acetate (100 mL) and saturated aqueous NaHCO3 (100 mL). The aqueous phase was separated, acidified to pH 3-4 with 10% aqueous H2SO4, and extracted with ethyl acetate (3×). After drying with Na2SO4, the solvent was removed in vacuo and the residue chromatographed (eluting with 1% acetic acid/ethyl acetate) to yield 1.56 g of the title compound as a white solid; MS(FAB+) m/e 387 (M+H)+. 1H NMR(DMSO-d6, 300 MHz) δ0.65 (m, 6H), 1.23-1.80 (m, 3H), 1.90 (m, 1H), 2.12 (m, 1H), 2.77-3.48 (m, 6H), 3.51 (m, 3H), 4.98 (m, 1H), 6.92 (m, 3 H), 7.28 (d, 1H), 7.97 (d, 1H), 10.90 (br s, 1H), 12.70 (br s, 1H).

Provenance & Evidence