|
With palladium on activated carbon; hydrogen; In ethyl acetate; for 2h; |
To a stirred solution of unsaturated ester 25 (4.13 g, 18.6 mmol) in ethyl acetate (30 mL) wasadded 10% palladium on activated carbon (0.4 g, 10% w/w). The solution was flushed with anatmosphere of hydrogen and stirred for 2 h. The reaction mixture was then filtered through a plug ofcelite and washed with ethyl acetate, solvent was then removed in vacuo to give saturated ester 28(3.9 g, 94%) as a yellow oil which was then used without further purification. To a stirred solution ofphenol 28 (3.75 g, 16.7 mmol) in acetonitrile (40 mL), under an atmosphere of nitrogen, was addedK2CO3 (6.9 g, 50.0 mmol) and stirred for 10 min. Benzyl bromide (6.0 mL, 50.0 mmol) was then addedand the resulting mixture allowed to stir for 65 h. The reaction mixture was then quenched withaddition of water (50 mL) and extracted with CH2Cl2 (3 × 30 mL). The organic phases were combined,washed with water (2 × 10 mL) and dried (MgSO4). Solvent was then removed in vacuo and the crudeproduct purified by column chromatography (9:1 hexanes, ethyl acetate) to give benzyl ether 29 (4.38g, 83%) as a colourless oil which was used immediately. To a stirred solution of ester 29 (4.3 g, 13.7mmol) in methanol (30 mL) was added aqueous NaOH (55 mL, 1M, 4 eq.) and stirred for 2.5 h. Themixture was then acidified with aqueous 2M HCl, extracted with ethyl acetate (3 × 50 mL), dried(MgSO4) and solvent removed in vacuo to give the title compound 32 (3.85 g, 98%) as a white solid.Rf = 0.30 (2:1 hexanes, ethyl acetate). Melting point: 99-100C. deltaH (400 MHz; CDCl3) 2.66 (2H, t, J = 7.7Hz, 2-H), 2.90 (2H, t, J = 7.7 Hz, 3-H), 3.88 (3H, s, 3?-OCH3), 5.13 (2H, s, 7?-H), 6.68 (1H, dd, J = 8.2, 2.0Hz, 6?-H), 6.76 (1H, d, J = 2.0 Hz, 2?-H), 6.81 (1H, d, J = 8.2 Hz, 5?-H), 7.27-7.32 (1H, m, 11?-H), 7.34-7.39 (2H, m, 10?-H), 7.41-7.45 (2H, m, 9?-H). deltaC (100 MHz; CDCl3) 30.4 (C-2), 35.9 (C-3), 56.1 (3?-OCH3), 71.3 (C-7?), 112.4 (C-2?), 114.5 (C-5?), 120.3 (C-6?), 127.4 (C-9?), 127.9 (C-11?), 128.7 (C-10?), 133.5 (C-1?),137.4 (C-8?), 146.9 (C-4?), 149.8 (C-3?), 178.8 (C-1). Values are in agreement with literature data [48]. |
10.2 g |
With palladium 10% on activated carbon; hydrogen; In ethanol; |
10% Pd/C (1.2 g) was added to a solution of 1.318,30 (Z,E isomer mixture, 11.8 g, 56.0 mmol) in EtOH (120 mL). The flask was flushed with hydrogen (balloon) several times, then kept under a slight pressure of H2 (balloon), and the mixture was stirred overnight by which time the reaction was(tlc, silica, 1:4 EtOAc-hexane). The mixture was diluted with EtOH and passed through a short pad of Celite. Evaporation of the filtrate gave 1.4 (10.2 g, 86%) as an oil which was pure enough for the next step. The material had: 1H NMR (CDCl3, 400 MHz) d 1.24 (t, J = 7.2 Hz, 3 H), 2.59 (t, J = 7.2 Hz, 2 H), 2.88 (t, J = 7.6 Hz, 2 H), 3.87 (s, 3 H), 4.13 (q, J = 7.2 Hz, 2 H), 5.48 (s, OH), 6.69 (dd, J = 2.0, 8.0 Hz, 1 H), 6.71 (d, J = 2.0 Hz, 1 H), 6.83 (d, J = 8.0 Hz, 1 H). |