METHYL1H-PYRROLE-2-CARBOXYLATE

To a solution of pyrrole-2-carboxylic acid (1) (16.65 g, 0.15 mol)in 10 mL of MeOH was added 50 mL of SOCl2 dropwise within30 min at 0 C. Subsequently, the reaction mixture was stirred at35 C for 24 h. Then, the solvent was evaporated in vacuo, andthe residue was purified by column chromatography using ethylacetate/petroleum ether as eluent, giving intermediate 2 as a whitesolid, yield 85percent, mp: 72–73 C.Example 36-1 Method I Synthesis of 5-tert-Butyl-3-(3-p-tolyl-ureido)-1H-pyrrole-2-carboxylic acid methyl ester. (Example 24) [Show Image] Step 1; Chlorotrimethylsilane (17.9 mL, 141 mmol, 2.5 equiv) is added in one portion to a solution of pyrrole-2-carboxylic acid (6.28 g, 56.5 mmol) in dry methanol (100 mL) under NTo a solution of pyrrole-2-carboxylic acid (6.28 g, 56.5 mmol) in anh. MeOH (100 mL) under N2 at room temp. was added TMSCl (17.9 mL, 141 mmol, 2.5 equiv) in one portion. After stirring overnight, the reaction mixture was concentrated under reduced pressure, redissolved in CH2Cl2, washed with water, dried (Na2SO4) and concentrated to give methyl pyrrole-2-carboxylate as a tannish semi-crystalline solid (4.62 g, 65percent): 1H NMR (CDCl3) δ 3.86 (s, 3H), 6.29 (br q, 1H), 6.92 (br m, 1H), 6.96 (br m, 1H), 9.30 (br s, 1H). This material was used in the next step without further purification.In dry methanol (40 mL), sodium (0.14 g, 6.20mmol) was dissolved and trichloroacetyl-1H-pyrrole (8) (9.440 g, 44.43 mmol) was added insmall quantities over 30 min. Then the reaction mixture was stirred for additional 2 hours atroom temperature, and then the solvent was removed and resulting crystals were dissolved indiethyl ether (50 mL). Ether solution was washed with HCl (4 mL, 3 N) and then NaHCO3(10 mL) solution. Then the organic phase was dried over Na2SO4. After the filtration andevaporation of the solvent, the crude product was purified via column chromatography (SiO2, ethyl acetate/hexane, 2:3) and concentrated in vacuum to obtain methyl 1H-pyrrole-2-carboxylate 9 (4.83 g, 87percent) which was crystallized from ethyl acetate/hexane as colorlesspelletsTo a freshly prepared solution of NaOCHTo a stirred solution of 11 (31.87 g, 0.150 mol) in methanol (50 mL) was added a solution of NaOMe solution in methanol (50 mL), prepared by dissolving of Na (3.46 g, 0.150 mol) in methanol, dropwise at 0 °C for 3 h. The solvent was evaporated and diluted HCl (50 mL) was added to residue. The mixture was extracted with ethyl acetate (3 × 150 mL) and dried over MgSO4. Evaporation of solvent gave the ester 12 as a brown solid (16.5 g, 88percent).General procedure: To an aqueous solution of βcyclodextrin (1.0 mmol of β-CD in 5mL of water), IBX (2.0 mmol), N-benzylpyrrolidine (1.0 mmol) was added while stirring, and stirring was continued for the stipulated reaction time as shown in the table at room temperature. After completion of reaction as indicated by TLC, the reaction mixture was extracted with ethylacetate (3 X 5mL), the combined organic layers were washed with saturated brine solution, dried and concentrated in vacuum. The crude product was purified by column chromatography on silica gel using hexane/ethyl acetate (9:1) as an eluent.Sodium metal (6.9 g, 0.30 mol) was dissolved in anhydrous methanol (1.5 L) and then 2-(trichloroacetyl)pyrrole (223 g, 1.5 mol) dissolved in anhydrous methanol (500 mL) was added. The mixture was heated at reflux for 12 hour. The methanol was removed under reduced pressure and the product crystallized by pouring the residue into a 3:1 ice-water/methanol mixture (2 L). The light brown solid was collected by vacuum filtration and dried to afford 97.2 g (0.78 mol, 74percent) of the title compound. 1H-NMR (CDCl3): ' 7.00 (m, 1H), 6.79 (d, 1H), 6.15 (dd, 1H), 3.74 (s, 1H).

Molecular Weight:125.13
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:125.047678466
Monoisotopic Mass:125.047678466
Topological Polar Surface Area:42.1
Heavy Atom Count:9
Complexity:114
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes