Isobutyl acrylate → Isobutyl 3-[4-(diphenylmethylidene)piperidin-1-yl]propanoate
Reaktionsgleichung
[C:1]1([C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:20]([O:24][CH2:25][CH:26]([CH3:28])[CH3:27])(=[O:23])[CH:21]=[CH2:22]>C(O)C>[C:1]1([C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:8]2[CH2:9][CH2:10][N:11]([CH2:22][CH2:21][C:20]([O:24][CH2:25][CH:26]([CH3:28])[CH3:27])=[O:23])[CH2:12][CH2:13]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1Komponenten
4
Edukt 2
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Versuchsvorschrift
A solution of 20 (0.782 g, 3.14 mmol), isobutyl acrylate (0.56 mL, 3.89 mmol) and ethanol (5 mL) was shaken at 75° C. for 2 h, then evaporated to dryness to give 1.04 g of 11e as a viscous yellow oil that was used without further purification. The structure was confirmed by 1H NMR. (Propanoate esters 11b, 11c, and 11f were similarly prepared (see synthesis of cyclopentyl acrylate in the Scheme 6). Isopropyl 3-[4-(diphenylmethylidene)piperidin-1-yl]propanoate (11d). Sodium hydride (60% dispersion in mineral oil, about 15 mg) was added to a stirred solution of 11b (1.20 g, 3.5 mmol) in 2-propanol (15 mL). Although after 1 h there was no insoluble solid, TLC showed evidence of degradation to the acid 11a, and the mixture was then stirred for an additional 48 h. The mixture was concentrated, suspended in a small amount of 1:1 heptane:ethyl acetate, filtered to remove insoluble solid (323 mg, 11a) and purified by flash chromatography to yield 560 mg (43%) of 11d. The structures were confirmed by 1H NMR and LC/MS. (Propanoate ester 11f was similarly prepared (this represents a second method for preparing 11f).) Cyclopentyl 3-[4-(diphenylmethylidene)piperidin-1-yl]propanoate, oxalic acid salt (11f-Ox). A solution of oxalic acid (190 mg, 2.11 mmol) in ethanol (3 mL) was added in one aliquot to a stirred solution of 11f (885 mg, 2.26 mmol) in warm ethanol (5.5 mL). The mixture became solid after 10 seconds of stirring. The solid mass was broken up and after 1.5 h of stirring, the solid was collected by suction filtration and washed with ethanol. After drying, the oxalate salt 11f-Ox was obtained as white powder (961 mg, 96%). 1H NMR, MS, and elemental analyses were consistent with the structure of the product. (The oxalate salt of 11d was similarly prepared.) Ethyl 3-[4-(diphenylmethylidene)piperidin-1-yl]propanoate, HCl salt (11c-HCl). 2 M HCl/ether (1.45 mL) was added to a stirred solution of 11c (812 mg, 2.32 mmol) in isopropyl ether (40 mL). After stirring for 30 min, the resulting precipitate was filtered, washed with isopropyl ether, and recrystallized from boiling H2O (2 mL) to give 608 mg of the hydrochloride salt of 11c-HCl as a creamy white powder. The structure was confirmed by 1H NMR, MS, and elemental analysis. (The HCl salt of 11e was similarly prepared.)