((3As,5r,6s,6as)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)(morpholino)methanone → [4-bromo-3-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-phenyl]-((3aS,5R,6S,6aS)-6-hydroxy-2,2-dimethyl-tetrahydro-furo[2,3-d][1,3]dioxol-5-yl)-methanone

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

Step-V: To a cooled solution of ((3aS,5R,6S,6aS)-6-Hydroxy-2,2-dimethyl-tetrahydro-furo[2,3-d][1,3]dioxol-5-yl)-morpholin-4-yl-methanone (11.05 g, 256 mmol) in THF (200 ml) was added 2.0 M solution of isopropylmagnesium chloride (12.78 ml, 256 mmol) under stirring at 0° C. and stirred for additional 1.5 h. To this was added a solution of 6-(2-bromo-5-iodo-benzyl)-2,3-dihydro-benzo[1,4]dioxine (4.0 g, 146 mmol) in THF (50 ml) at 0° C. and then stirred at room temperature for 2 h. The reaction mixture was quenched by the addition of aqueous saturated ammonium chloride solution and extracted with ethyl acetate (200 ml×3). Combined organic layers were washed with brine (500 ml), dried over sodium sulfate, concentrated and purified by silica gel column chromatography to give 4.7 g of [4-bromo-3-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-phenyl]-((3aS,5R,6S,6aS)-6-hydroxy-2,2-dimethyl-tetrahydro-furo[2,3-d][1,3]dioxol-5-yl)-methanone. 1H NMR (400 MHz, CDCl3): δ 1.35 (s, 3H), 1.53 (s, 3H), 2.92 (d, J=4.0 Hz, 1H), 4.04 (d, J=3.6 Hz, 2H), 4.23 (s, 4H), 4.54 (br s, 1H), 4.56 (d, J=3.6 Hz, 1H), 5.21 (d, J=2.8 Hz, 1H), 6.05 (d, J=3.2 Hz, 1H), 6.67 (s, 2H), 6.79 (d, J=9.2 Hz, 1H), 7.68 (d, J=9.2 Hz, 1H), 7.75-7.77 (m, 2H). MS (ES) m/z 490.7 (M+1).

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