反应详情

A flask charged with a stir bar and anhydrous LiCl (49 mg) is heated to 180° C. under high vacuum (ca. 1 mbar). After 30 min the flask is cooled to room temperature, filled with Ar, and Zn powder (84 mg) is added under Ar atmosphere. The flask is reevacuated (ca. 1 mbar) and heated to 180° C. After another 30 min the flask is cooled to room temperature and filled with Ar again. Tetrahydrofuran (dry, 0.5 mL) is added and the Zn is activated with 1,2-dibromoethane (2 μL) and trimethylsilyl chloride (1.5 μL) (for comparison see e.g. Synthesis 2009, 681-6). A solution of 2,6-dimethylbenzyl bromide (0.23 g) in tetrahydrofuran (dry, 2 mL) is added dropwise. The mixture is stirred for 30 min prior to addition of {(S)-6-[(R)-4-bromo-5-cyano-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester (0.10 g) in tetrahydrofuran (dry, 2 mL) and [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]-(3-chloropyridyl)-palladium(II) dichloride (Pd-PEPPSI-IPr, 20 mg). The mixture is heated to 60° C. and stirred at this temperature overnight. After cooling to room temperature, aqueous NH4Cl solution is added and the resulting mixture is extracted with ethyl acetate. The combined extracts are dried (MgSO4) and concentrated. The residue is purified by HPLC on reversed phase (MeCN/water/NH4OH) to give the title compound. LC (method 4): tR=1.28 min; Mass spectrum (ESI+): m/z=468 [M+H]+.

1. additionA flask charged with a stir bar
2. additionis added under Ar atmosphere
3. temperatureheated to 180° C
4. temperatureAfter another 30 min the flask is cooled to room temperature
5. additionfilled with Ar again
6. temperatureThe mixture is heated to 60° C.
7. stirringstirred at this temperature overnight
8. temperatureAfter cooling to room temperature
9. extractionthe resulting mixture is extracted with ethyl acetate
10. dry with materialThe combined extracts are dried (MgSO4)
11. concentrationconcentrated
12. customThe residue is purified by HPLC on reversed phase (MeCN/water/NH4OH)