Tetrahydrofuran → Gamma-Butyrolactone
Reaction equation
[C:1]([C:9]1[NH:10][CH:11]=[CH:12][CH:13]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+:15].[O:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1>>[Na:15][N:10]1[CH:11]=[CH:12][CH:13]=[C:9]1[C:1](=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[C:20]1(=[O:8])[O:16][CH2:17][CH2:18][CH2:19]1Participants
5
Procedure
A solution of 2-benzoylpyrrole (II, 20.0 g, 117 mmoles) in 50 mL of anhydrous tetrahydrofuran was added dropwise to a nitrogen blanketed stirred suspension of sodium hydride (129 mmoles) in 300 mL of anhydrous tetrahydrofuran over the course of 30 minutes. The reaction mixture was stirred under a nitrogen atmosphere for 1 hour after which gas evolution had ceased. The tetrahydrofuran was then evaporated under reduced pressure to leave the 1-sodio-2-benzoylpyrrole as a yellow solid gamma-Butyrolactone (11.0 g, 128 mmoles) was added to the solid and this mixture was protected from moisture with a calcium sulfate drying tube and heated to 135° C. for 5 hours. After being cooled to room temperature, the resulting solid was dissolved in 1% aqueous sodium hydroxide (500 mL) and extracted with ethyl ether (2×300 mL). The aqueous phase was then acidified to pH 2 by dropwise addition of concentrated hydrochloric acid with vigorous stirring. The acidified aqueous solution was extracted with two portions of ethyl acetate (350 mL, 150 mL) and the combined ethyl acetate extracts were dried over anhydrous sodium sulfate and evaporated under reduced pressure to give 4-(2-benzoylpyrrol-1-yl)butyric acid (III, 27.61 g, 92%). 1H NMR (CDCl3): delta 2.18 (m, 2H), 2.40 (t, J=7 Hz), 4.48 (t, J=7 Hz, 2H), 6.17 (m, 1H), 6.75 (m, 1H); 6.99 (m, 1H), 7.41-7.55 (complex m, 3H), 7.77 (m, 2H). This acid was of sufficient purity to proceed with the esterification step without further purification.