Acetic Acid → ethyl 5-formyl-3-methyl-1H-pyrrole-2-carboxylate

HRID 397413Notes

Reaction equation

C(O)(=[O:3])C.[CH3:5][C:6]1[CH:10]=[C:9]([CH3:11])[NH:8][C:7]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13]>C1COCC1.O>[CH2:15]([O:14][C:12]([C:7]1[NH:8][C:9]([CH:11]=[O:3])=[CH:10][C:6]=1[CH3:5])=[O:13])[CH3:16]

Participants

Conditions

Temperature: -7.5 °C

Procedure

Acetic acid (360 mL) and water (300 ml) was added to a solution of ethyl 3,5-dimethyl-2-pyrrolecarboxylate (5 g, 29.9 mmol) in THF (300 mL). The mixture was cooled to −10 to −5° C. for 30 minutes. To the mixture was then added ceric ammonium nitrate (CAN, 67.21 g, 122.6 mmol) over a period of 30 minutes. The mixture was stirred at −10 to −5° C. for 1.5 hours. The reaction was diluted with water (800 mL) and extracted with dichloromethane (3×). The combined extracts were washed with sodium bicarbonate solution until the aqueous layer was basic, dried and concentrated. The residue was purified on a silica gel column (10% EtOAc in hexane) to give 2.4 g (44%) of 5-formyl-3-methyl-1H-pyrrole-2-carboxylic acid ethyl ester as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 12.61 (br s, 1H, NH), 9.64 (s, 1H, CHO), 6.78 (s, 1H), 4.27 (q, J=7.17 Hz, 2H, OCH2CH3), 2.26 (s, 3H, CH3), 1.30 (t, J=7.17 Hz, 3H, OCH2CH3). MS 182 [M++1].

Workup

extractionextracted with dichloromethane (3×)
washThe combined extracts were washed with sodium bicarbonate solution until the aqueous layer
customdried
concentrationconcentrated
customThe residue was purified on a silica gel column (10% EtOAc in hexane)

Sources & evidence

ORD record: ord-f3fc8d85b2bd48d6aee0329a06a3a6ec
Source dataset: uspto-grants-2003_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06610688B2

Reaction notes

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