2-(bromomethyl)-1,3-dimethylbenzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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]+. A flask charged with a stir bar is added under Ar atmosphere heated to 180° C After another 30 min the flask is cooled to room temperature filled with Ar again The mixture is heated to 60° C. stirred at this temperature overnight After cooling to room temperature the resulting mixture is extracted with ethyl acetate The combined extracts are dried (MgSO4) concentrated The residue is purified by HPLC on reversed phase (MeCN/water/NH4OH)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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]+. A flask charged with a stir bar is added under Ar atmosphere heated to 180° C After another 30 min the flask is cooled to room temperature filled with Ar again The mixture is heated to 60° C. stirred at this temperature overnight After cooling to room temperature the resulting mixture is extracted with ethyl acetate The combined extracts are dried (MgSO4) concentrated The residue is purified by HPLC on reversed phase (MeCN/water/NH4OH)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from 3-(3-Benzyl-8-trifluoromethyl-quinolin-4-yl)-phenol and 2-Bromomethyl-1,3-dimethyl-benzene following the procedure of Example 478: MS m/z 498; HRMS: calcd for C32H26F3NO+H+, 498.20392; found (ESI, [M+H]+), 498.2038.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from [4-(3-hydroxyphenyl)-8-(trifluoromethyl)quinolin-3-yl](phenyl)methanone and 2-Bromomethyl-1,3-dimethylbenzene following the procedure of Example 478: MS (ES) m/z 511.5.