((3As,5r,6s,6as)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)(morpholino)methanone → (3-(4-chlorobenzyl)-4-methylphenyl)((3aS,5R,6S,6aS)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]-dioxol-5-yl)methanone

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a solution of ((3aS,5R,6S,6aS)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)(morpholino)methanone (25.3 g, 92.6 mmol) in THF (200 mL) under nitrogen at 0° C. was added tert-butyl magnesium chloride (1 M in THF, 100 mL, 100 mmol). This solution was stirred at 0° C. for 30 minutes. Meanwhile, a solution of 4-bromo-2-(4-chlorobenzyl)-1-methylbenzene (3, 32.9 g, 111.1 mmol) in THF (330 mL) under nitrogen was cooled to −78° C. n-Butyllithium (2.5 M in hexanes, 48 mL, 120 mmol) was added dropwise via syringe and stirred for 10 min. The magnesium alkoxide solution was transferred via cannula into the aryllithium solution at −78° C. The reaction was stirred for 30 min at −78° C., allowed to warm to room temperature and stirred for 60 min, quenched with 500 mL of a 1:1 (v:v) solution of saturated aqueous NH4Cl/brine. The aqueous layer was extracted two times with 300 mL of EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated under vacuum. The crude residue was taken up in 100 mL of EtOAc and heated until most of the solids dissolved. 250 mL of hexanes was added and the flask was chilled in an ice bath for two hours. The white precipitate was filtered off and washed with 20% EtOAc/hexane, providing the title compound as a white solid (26.09 g, 70% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.88 (dd, J=7.8, 1.8 Hz, 1 H), 7.76 (d, J=1.5 Hz, 1 H), 7.29 (d, J=8.1 Hz, 1 H), 7.26 (d, J=8.3 Hz, 2 H), 7.05 (d, J=8.3 Hz, 2 H), 6.08 (d, J=3.8 Hz, 1 H), 5.28 (d, J=2.8 Hz, 1 H), 4.59 (d, J=3.5 Hz, 1 H), 4.57 (t, J=3.2 Hz, 1 H), 4.01 (s, 2 H), 3.06 (d, J=4.0 Hz, 1 H), 2.30 (s, 3 H), 1.37 (s, 3 H). MS (ES+) [M+H]+=403.

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