Tetrahydrofuran → tert-butyl N-Boc-4-methylene-L-prolinate

反応式

[H-].[Na+].[C:3]([O:7][C:8](=[O:22])[C@@H:9]1[CH2:13][C:12](=O)[CH2:11][N:10]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])([CH3:6])([CH3:5])[CH3:4].[CH2:23]1COCC1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:3]([O:7][C:8](=[O:22])[C@@H:9]1[CH2:13][C:12](=[CH2:23])[CH2:11][N:10]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])([CH3:6])([CH3:5])[CH3:4]

参加物

実験手順

To an oven-dried 2-necked round-bottomed flask was added sodium hydride (80% oil dispersion) (497 mg, 16.56 mmol) followed by dry tetrahydrofuran (42 mL) and methyltriphenyl-phosphonium bromide (5.92 g, 16.56 mmol). The suspension was stirred for 4 hours at 50° C., at which time a solution of 1-(tert-butyloxycarbonyl)-4-oxo-L-proline tert-butyl ester (1.18 g, 4.14 mmol) in THF (10 mL) was added dropwise with stirring over 30 minutes. The reaction mixture was stirred for 2 hours at 50° C., cooled, filtered, and evaporated. The residue was taken up in ethyl acetate (100 mL), washed with N hydrochloric acid (2×), water (2×), saturated brine solution, dried (Na2SO4), and evaporated. The crude product was subjected to flash silica gel chromatography eluting with 15% diethyl ether/hexane. The title compound was obtained as a colorless oil; yield 519 mg (43%). 400 MHz 1HNMR (CDCl3): δ1.42-1.47 (3s, 18H); 2.54 (m, 1H); 2.92 (m, 1H); 4.03 (m, 2H); 4.23-4.38 (m, 1H); 4.98 (m, 2H).