Thiazole → Ethyl (E)-4-[2-(5,5-dimethyl-8-(thiazol-2-yl)-5,6-dihydronaphthalen-2-yl)ethenyl]-benzoate

To a cold (−78° C.) solution of thiazole (0.38 g (0.10 mL, 1.4 mmol) in THF (2.0 mL) was added n-butyl lithium (1.6 M solution in hexanes, 0.5 mL, 0.8 mmol) and stirred for 30 min. To this solution was added a 0.176 g (1.3 mmol) of zinc chloride in 3.0 mL of tetrahydrofuran and stirred for 45 min. The resulting turbid solution was transferred, via cannula, to a flask containing a mixture of 0.17 g (0.35 mmol) of ethyl (E)-4-[2-(5,5-dimethyl-8-(trifluoromethylsulfonyl)oxy-5,6-dihydronaphthalen-2-yl)ethenyl] benzoate (Compound A9) and 15 mg (0.01 mmol) of tetrakis(triphenylphosphine)palladium(0) in 3.0 mL of tetrahydrofuran. The reaction mixture was stirred for 1 h at ambient temperature and 1.5 h at 55° C. The reaction mixture was treated with aqueous NH4Cl, and extracted with EtOAc (2×). The combined organic layer was washed with brine and dried (MgSO4). The solvent was removed under reduced pressure and the crude product was purified by flash chromatography (silica, 20% ethyl acetate in hexane) to afford the title compound as a white solid.

1. stirringstirred for 45 min
2. customThe resulting turbid solution was transferred, via cannula, to a flask
3. additioncontaining
4. stirringThe reaction mixture was stirred for 1 h at ambient temperature and 1.5 h at 55° C
5. extractionextracted with EtOAc (2×)
6. washThe combined organic layer was washed with brine
7. dry with materialdried (MgSO4)
8. customThe solvent was removed under reduced pressure
9. customthe crude product was purified by flash chromatography (silica, 20% ethyl acetate in hexane)

ORD record

ord-13aa27f0673b458eb6846e7b383d1f90

Source dataset

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06855832B2