Potassium Carbonate → Trans-2-(2-(Trifluoromethyl)Cyclopropyl)Naphthalene

Temperature

100 °C

In an open vial with pressure-release top, a stirred mixture of 2-naphthyltrifluoromethanesulfonate (Aldrich, St. Louis, Mo.) (69 mg, 0.25 mmol), palladium(II) acetate (5.5 mg, 0.025 mmol), 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (23 mg, 0.05 mmol), K2CO3 (138 mg, 1.0 mmol) and trans-2-(trifluoromethyl)cyclopropylboronic acid MIDA ester (99 mg, 0.38 mmol) in toluene (2.5 mL) and H2O (0.5 mL) was de-gassed with N2 for 15 minutes, then the reaction mixture placed under nitrogen, sealed and heated to 100° C. and stirred for 6 hours. After allowing to cool, the reaction mixture was diluted with H2O (15 mL) and EtOAc (20 mL), filtered through Celite and the filter cake washed with EtOAc (2×20 mL). The filtrate was partitioned and the aqueous layer extracted with EtOAc (2×15 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under vacuum to leave a crude residue. The residue was purified by preparative thin-layer chromatography (2 prep TLC plates used) using EtOAc/hexane (1:99) as eluent to give the product (45.9 mg, 78%) as a solid.

1. customwas de-gassed with N2 for 15 minutes
2. customsealed
3. temperatureto cool
4. additionthe reaction mixture was diluted with H2O (15 mL) and EtOAc (20 mL)
5. filtrationfiltered through Celite
6. washthe filter cake washed with EtOAc (2×20 mL)
7. customThe filtrate was partitioned
8. extractionthe aqueous layer extracted with EtOAc (2×15 mL)
9. dry with materialThe combined organic extracts were dried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated under vacuum
12. customto leave a crude residue
13. customThe residue was purified by preparative thin-layer chromatography (2 prep TLC plates used)

ORD record

ord-30e10124aa844d149de1332310214659

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09108990B2