methyl 5-[3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]-1H-pyrrole-2-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 5-(3-tert-butoxy-3-oxopropyl)-1H-pyrrole-2-carboxylate (14.8 g, 58.4 mmol) was treated with 4 N HCl (100 mL) at rt for about 12 h. The solvent was removed and the white solid product was dried to give 12.8 g (94%) of 3-(5-(methoxycarbonyl)-1H-pyrrol-2-yl)propanoic acid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.73 (t, J=6.81 Hz, 2H), 2.98 (t, J=6.79 Hz, 2H), 3.83 (s, 3H), 6.01 (dd, J=3.59, 2.61 Hz, 1H), 6.83 (dd, J=3.61, 2.63 Hz, 1H), 9.70 (br s, 1H); LCMS-MS (ESI+) 198.2 (M+H). The solvent was removed the white solid product was dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (z)-methyl 5-(3-tert-butoxy-3-oxoprop-1-enyl)-1H-pyrrole-2-carboxylate or (E)-methyl 5-(3-tert-butoxy-3-oxoprop-1-enyl)-1H-pyrrole-2-carboxylate (13.6 g, 54.1 mmol, 2 equal batches) in EtOAc (200 mL) under nitrogen was added 10% Pd/C. The flask was flushed with hydrogen three times before allowing the reaction to stir under hydrogen for about 18 h. The catalyst was filtered off using Celite and the filtrate was concentrated to give 27.4 g methyl 5-(3-tert-butoxy-3-oxopropyl)-1H-pyrrole-2-carboxylate as a white solid (100%) for each stereoisomer. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.46 (s, 9H), 2.54-2.59 (m, 2H), 2.90 (t, J=6.83 Hz, 2H), 3.83 (s, 3H), 5.97 (dd, J=3.49, 2.86 Hz, 1H), 6.81 (dd, J=3.61, 2.59 Hz, 1H), 9.30 (br s, 1H); LCMS-MS (ESI+) 197.86 (M-isobutylene). The flask was flushed with hydrogen three times the reaction The catalyst was filtered off the filtrate was concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (z)-methyl 5-(3-tert-butoxy-3-oxoprop-1-enyl)-1H-pyrrole-2-carboxylate or (E)-methyl 5-(3-tert-butoxy-3-oxoprop-1-enyl)-1H-pyrrole-2-carboxylate (13.6 g, 54.1 mmol, 2 equal batches) in EtOAc (200 mL) under nitrogen was added 10% Pd/C. The flask was flushed with hydrogen three times before allowing the reaction to stir under hydrogen for about 18 h. The catalyst was filtered off using Celite and the filtrate was concentrated to give 27.4 g methyl 5-(3-tert-butoxy-3-oxopropyl)-1H-pyrrole-2-carboxylate as a white solid (100%) for each stereoisomer. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.46 (s, 9H), 2.54-2.59 (m, 2H), 2.90 (t, J=6.83 Hz, 2H), 3.83 (s, 3H), 5.97 (dd, J=3.49, 2.86 Hz, 1H), 6.81 (dd, J=3.61, 2.59 Hz, 1H), 9.30 (br s, 1H); LCMS-MS (ESI+) 197.86 (M-isobutylene). The flask was flushed with hydrogen three times the reaction The catalyst was filtered off the filtrate was concentrated

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 5-(3-tert-butoxy-3-oxopropyl)-1H-pyrrole-2-carboxylate (14.8 g, 58.4 mmol) was treated with 4 N HCl (100 mL) at rt for about 12 h. The solvent was removed and the white solid product was dried to give 12.8 g (94%) of 3-(5-(methoxycarbonyl)-1H-pyrrol-2-yl)propanoic acid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.73 (t, J=6.81 Hz, 2H), 2.98 (t, J=6.79 Hz, 2H), 3.83 (s, 3H), 6.01 (dd, J=3.59, 2.61 Hz, 1H), 6.83 (dd, J=3.61, 2.63 Hz, 1H), 9.70 (br s, 1H); LCMS-MS (ESI+) 198.2 (M+H). The solvent was removed the white solid product was dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (z)-methyl 5-(3-tert-butoxy-3-oxoprop-1-enyl)-1H-pyrrole-2-carboxylate or (E)-methyl 5-(3-tert-butoxy-3-oxoprop-1-enyl)-1H-pyrrole-2-carboxylate (13.6 g, 54.1 mmol, 2 equal batches) in EtOAc (200 mL) under nitrogen was added 10% Pd/C. The flask was flushed with hydrogen three times before allowing the reaction to stir under hydrogen for about 18 h. The catalyst was filtered off using Celite and the filtrate was concentrated to give 27.4 g methyl 5-(3-tert-butoxy-3-oxopropyl)-1H-pyrrole-2-carboxylate as a white solid (100%) for each stereoisomer. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.46 (s, 9H), 2.54-2.59 (m, 2H), 2.90 (t, J=6.83 Hz, 2H), 3.83 (s, 3H), 5.97 (dd, J=3.49, 2.86 Hz, 1H), 6.81 (dd, J=3.61, 2.59 Hz, 1H), 9.30 (br s, 1H); LCMS-MS (ESI+) 197.86 (M-isobutylene). The flask was flushed with hydrogen three times the reaction The catalyst was filtered off the filtrate was concentrated