Water → Methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

HRID 601794Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[NH:9][C:8]([CH2:10][CH2:11][C:12]([OH:14])=O)=[CH:7][CH:6]=1)=[O:4].O.C(=O)(O)[O-].[Na+]>ClCCCl>[O:14]=[C:12]1[C:7]2[CH:6]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[NH:9][C:8]=2[CH2:10][CH2:11]1

Participants

Conditions

Temperature: 100 °C

Procedure

A suspension of polyphosphoric acid (115%, 109 g) and powdered 3-(5-(methoxycarbonyl)-1H-pyrrol-2-yl)propanoic acid (12.1 g, 51.8 mmol) in 1,2-dichloroethane (40 mL) was heated for 1 h at 100° C. with occasional mixing with a large spatula. Water (100 mL) was added and the mixture was carefully poured into a large Erlenmeyer flask containing solid sodium bicarbonate and ice. The reaction was neutralized (pH 7) and then extracted with EtOAc (5×150 mL). The combined organic extracts were washed with water, NaHCO3, brine, dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography (0-80% EtOAc/Heptane) to afford 8.0 g of methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (86%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.93-2.98 (m, 2H), 2.99-3.04 (m, 2H), 3.90 (s, 3H), 6.98 (d, J=1.71 Hz, 1H), 9.42 (br s, 1H); LCMS-MS (ESI+) 180.0 (M+H).

Workup

additionwith occasional mixing with a large spatula
additionthe mixture was carefully poured into a large Erlenmeyer flask
extractionextracted with EtOAc (5×150 mL)
washThe combined organic extracts were washed with water, NaHCO3, brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by flash chromatography (0-80% EtOAc/Heptane)

Sources & evidence

ORD record: ord-751b7e6f6b444de58a7a8ada4debf1f2
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07902252B2

Reaction notes

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