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Copyright © 2012 Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys ® is a trademark owned and protected by Elsevier Properties SA and used under license. 1/3 2012-03-09 02:04:15 Query Query Results Date 1. Query OH O O O 1 reactions 2012-03-09 02h:00m:46s (EST) Search as: Product, As drawn, No salts, No mixtures Copyright © 2012 Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys ® is a trademark owned and protected by Elsevier Properties SA and used under license. 2/3 2012-03-09 02:04:15 O O O O Br OH O O O Rx-ID: 24428051 View in Reaxys 1/1 Yield Conditions & References 52 % Example Title 4.4. Synthesis of intermediate[26] and [27] A THF solution (15 mL) of 1-bromo-4-phenoxybenzene (2.48 g, 10 mmol) was added dropwise to a mixture of Mg (288 mg, 12 mmol) and a small amount of iodine in anhydrous THF (10 mL). After refluxing for 1 h, the Grignard reagent of (4-phenoxyphenyl)magnesium bromide was obtained, which was dissolved in THF and added dropwise to a cooled (-78 .deg.C) solution of ethyl pyruvate (1.16 g, 10 mmol). After completion of the addition, the reaction temperature was slowly allowed to rise to 20 .deg.C and kept overnight. The reaction mixture was poured into an ice solution of HCl and then extracted with methylene chloride (3 .x. 40 mL). The methylene chloride extract was washed with brine (30 mL) and dried with MgSO4. Evaporation of methylene chloride at reduced pressure afforded the crude product. After puri- fication by flash column chromatography, the intermediate 7 (1.49 g) was obtained as a pale yellow oil in a yield of 52percent. 1H NMR (600 MHz, CDCl3): δ 1.27 (t, J = 7.2 Hz, 1H, CH3), 1.77 (s, 3H, CH3), 3.78 (s, 1H, OH), 4.22-4.27 (m, 2H, CH2), 6.97 (d, J = 9.0 Hz, 2H, ArH), 7.01 (d, J = 7.8 Hz, 2H, ArH), 7.11 (t, J = 7.5 Hz, 1H, ArH), 7.34 (t, J = 7.8 Hz, 2H, ArH), 7.51 (d, J = 8.4 Hz, 2H, ArH). Stage 1: With iodine, magnesium in tetrahydrofuran, Time= 1h, Reflux Stage 2: in tetrahydrofuran, T= -78 - 20 °C , Grignard reaction Stage 3: With hydrogenchloride in tetrahydrofuran, water, Cooling with ice Wang, Fu; Li, Hui; Yang, Wen-Chao; Yang, Guang-Fu; Wang, Le; Wu, Jia-Wei; Bioorganic and Medicinal Chemistry; vol. 19; nb. 15; (2011); p. 4608 - 4615 View in Reaxys Example Name 2 Example Title Ethyl 2-(4-phenoxyphenyl)lactate STR19 EXAMPLE 2 Ethyl 2-(4-phenoxyphenyl)lactate STR19 A 250-ml flask fitted with magnetic stirring, water condenser, 125 mL dropping funnel, thermometer, and nitrogen inlet was charged with 2.7 g (110 mmol) of magnesium metal and dried with a heat gun under strong nitrogen purge. After cooling, the funnel was charged with a solution of 17.5 mL (24.9 g, 100 mmol) of 4-bromodiphenyl ether in 67 mL of dry THF, and 10 mL was run into the flask. With stirring, the Grignard initiated spontaneously, and the rest of the bromide solution was added over 15 minutes, maintaining an internal temperature of 67.deg.-68.deg. C. When addition was complete, the temperature held at 68.deg. C. for 5 minutes, then began to drop, reaching 30.deg. C. after 45 minutes. Meanwhile, a 250 mL flask, magnetic stirrer, and 125 mL dropping funnel that had been oven dried were assembled hot under nitrogen and allowed to cool. A low-temperature thermometer was then added, the flask was charged with a solution of 11.5 mL (12.2 g, 105 mmol) of ethyl pyruvate in 66 mL of dry THF, and the solution of Grignard reagent was transferred to the dropping funnel by means of a syringe. The pyruvate solution was chilled to -10.deg. C., and the Grignard solution was run in over 15 minutes with good stirring, cooling to maintain an internal temperature of -5.deg. C. to -10.deg. C. The resulting solution was stirred and treated with 50 mL of water followed by 50 mL of saturated aqueous ammonium chloride, giving two clear phases. These were separated, and the upper phase was subjected to rotary evaporation to remove most of the THF. Addition of 50-mL portions of water and methylene chloride gave two clear phases. These were separated, the aqueous phase was washed with another 25 mL of methylene chloride, and the combined organic phases were washed with water and brine, dried over magnesium sulfate,, and evaporated to leave 23.8 g of yellow-orange oil. Kugelrohr distillation at 140.deg. C./0.1-0.2 mm for 60 minutes removed volatile impurities, leaving 17.1 g (60percent) of the product as a clear orange oil: nD 26 1.5555; IR (neat) 3490, 1725 cm-1; NMR (CDCl3, 200 MHz) 1.3 (3H, t, J=7), 1.8 (3H, s), 3.8 (1H, broad s), 4.2 (2H, m), 6.9-7.0 (4H, m), 7.1 (1H, t, J=7), 7.3 (2H, t, J=7), 7.5 (2H, d, J=9). With nitrogen in tetrahydrofuran, dichloromethane, water Patent; E. I. Du Pont de Nemours and Company; US5223523; (1993); (A1) English View in Reaxys Copyright © 2012 Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys ® is a trademark owned and protected by Elsevier Properties SA and used under license. 3/3 2012-03-09 02:04:15