Cesium carbonate → (+/-)-3-[4-(4'-Trifluoromethyl-biphenyl-3-ylmethoxy)-phenyl]-3-(3-methylthiophen-2-yl)-propionic acid

温度

50 °C

Benzyl chloride 2.3 (113 mg, 0.434 mmol) and phenol 54.1 (100 mg, 0.362 mmol) were dissolved in acetone (1 mL) and treated with Cs2CO3 (371 mg, 1.14 mmol). The reaction was stirred at 50° C. for 16 h, filtered and concentrated. The residue was purified by column chromatography (silica gel, 30% to 60% ethyl acetate in hexanes). Eluant containing desired compound was concentrated and dissolved in a THF/MeOH/2N LiOH(aq) (1:1:1) solution (2 mL). The mixture was stirred at room temperature for 90 min., the solution was poured into 0.65 N HCl(aq.) (2 mL). The aqueous phase was extracted with dichloromethane (3×10 mL) and the combined organic phases were dried over Na2SO4. After filtration and drying, 154 mg (0.311 mmol) of carboxylic acid 54 was obtained. 1H NMR (400 MHz) (CDCl3) δ 7.43-7.70 (m, 8H), 7.21 (d, 2H, J=8.6 Hz), 7.05 (d, 1H, J=5.0 Hz), 6.92 (d, 2H, J=8.6 Hz), 6.76 (d, 1H, 5.0 Hz), 5.09 (s, 2H), 4.74 (t, 1H, J=7.8 Hz), 3.05 (d, 2H, J=7.8 Hz), 2.15 (s, 3H).

1. filtrationfiltered
2. concentrationconcentrated
3. customThe residue was purified by column chromatography (silica gel, 30% to 60% ethyl acetate in hexanes)
4. additionEluant containing desired compound
5. concentrationwas concentrated
6. dissolutiondissolved in a THF/MeOH/2N LiOH(aq) (1:1:1) solution (2 mL)
7. stirringThe mixture was stirred at room temperature for 90 min.
8. additionthe solution was poured into 0.65 N HCl(aq.) (2 mL)
9. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
10. dry with materialthe combined organic phases were dried over Na2SO4
11. filtrationAfter filtration
12. customdrying

ORDレコード

ord-b980786450374ce79bba07f08fc3f3e1

出典データセット

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07649110B2