Water → Ethyl 1-(4-bromo-2-iodobenzyl)-4-(trifluoromethyl)cyclohexanecarboxylate

Temperature

-78 °C

Ethyl 4-(trifluoromethyl)cyclohexanecarboxylate (Intermediate 76, 1.492 g, 6.65 mmol) was dissolved in THF (25 mL). The atmosphere was exchanged to argon, and the solution was cooled to −78° C. Lithium diisopropylamide (1.8 M in THF/heptane/ethylbenzene) (4.07 mL, 7.32 mmol) was added, while the temperature was kept at −78° C. The solution was stirred for 30 min at −78° C. 4-Bromo-1-(bromomethyl)-2-iodobenzene (see Caruso, A.; Tovar, J., D. J. Org. Chem. 2011, 76, 2227-2239., 2.50 g, 6.65 mmol) in THF (25 mL) was added via a syringe. The mixture was allowed to reach r.t., while stirred for 2 h. Water (10 mL) was added to the reaction mixture, followed by EtOAc (40 mL). The phases were separated. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (eluent: heptane/EtOAc 95/5) to give the title compound (2.41 g, 69% yield): 1H NMR (400 MHz, CDCl3) δ ppm 1.22-1.27 (m, 3H) 1.29-1.43 (m, 4H) 1.82-1.90 (m, 2H) 1.82-1.90 (m, 3H) 1.97 (br. s., 2H) 2.28-2.36 (m, 3H) 3.01 (s, 3H) 4.18 (q, 3H) 6.91 (m, 1H) 7.38 (m, 1H) 7.99 (m, 1H); MS (ES+) m/z 520 [M+H]+.

1. customwas kept at −78° C
2. customto reach r.t.
3. stirringwhile stirred for 2 h
4. customThe phases were separated
5. dry with materialThe organic layer was dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash chromatography (eluent: heptane/EtOAc 95/5)

ORD record

ord-b9c08b499e164e2fa097d4e070de4f36

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09248129B2