Sodium Nitrite → Ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate

Temperature

90 °C

Ethyl 1-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate (1 g, 2.2 mmol) was dissolved in a mixture of MeCN/H2O/HCl 30 mL/30 mL/2 mL at 0° C. A solution of NaNO2 (0.200 g, 2.9 mmol) in water (10 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of CuCl (1.1 g, 11.1 mmol) in water (10 mL) was added drop wise at 0° C. The reaction mixture was heated to 90° C. for 2.0 h and the solvent was evaporated. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with water (50 mL) followed by brine (50 mL). The solution was dried over Na2SO4, filtered and concentrated under reduced pressure to give a crude black oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate as yellow oil (1.1 g).

1. customthe solvent was evaporated
2. extractionThe reaction mixture was extracted with EtOAc (3×50 mL)
3. washthe combined organic layers were washed with water (50 mL)
4. dry with materialThe solution was dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto give a crude black oil
8. customThe oil was purified by chromatography over silica gel (hexane/EtOAc)

ORD record

ord-f5e9515bcbe0494c9fb6900fb18431fa

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08664249B2