Hydrochloric Acid → HCID 57995544, compound

Temperature

2.5 °C

To a solution of 2-[6-amino-5-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-3-yl]-3-cyclobutyl-propionic acid methyl ester (14.7 g, 27.7 mmol) in a mixture of MeCN and H2O (120 mL/120 mL), concentrated HCl (25 mL) was added. The reaction mixture was cooled down to 0-5° C. and a solution of NaNO2 (2.9 g, 42.0 mmol) in water (3 mL) was added dropwise. The reaction mixture was stirred at 0-5° C. for 40 min and CuCl (I) (27 g, 272.7 mmol) was added at once. The reaction mixture was heated at 50° C. for additional 3 h and the solvent was evaporated. The reaction mixture was extracted with EtOAc (3×50 mL) and the combined organic phases were washed with water (200 mL) and brine (100 mL). The organic phase was dried over MgSO4 and evaporated to give the product (14.5 g, 95%) as a yellow oil. 1H NMR (300 MHz, CDCl3/TMS): δ 7.70 (d, J=8.2 Hz, 2H), 7.53 (d, J=8.0 Hz, 2H), 6.98 (dd, J=6.1, 1.6 Hz, 2H), 4.47 (q, J=8.0 Hz, 2H), 3.68 (s, 3H), 3.48 (t, J=7.7 Hz, 1H), 2.20-2.10 (m, 2H), 2.03-1.75 (m, 5H), 1.70-1.52 (m, 2H). 13C NMR (75 MHz, CDCl3/TMS): δ 173.6, 153.5, 142.2, 141.0, 138.9, 129.7, 125.0 (q, 3JCF=3.6 Hz), 124.8, 124.0 (q, 1JCF=271.6 Hz), 126.6 (q, 1JCF=278.8 Hz), 121.4, 114.0, 67.3 (q, 1JCF=35.4 Hz), 52.2, 49.3, 40.8, 34.0, 28.3, 28.0, 18.5.

1. additionwas added
2. temperatureThe reaction mixture was heated at 50° C. for additional 3 h
3. customthe solvent was evaporated
4. extractionThe reaction mixture was extracted with EtOAc (3×50 mL)
5. washthe combined organic phases were washed with water (200 mL) and brine (100 mL)
6. dry with materialThe organic phase was dried over MgSO4
7. customevaporated

ORD record

ord-a1f1d67e359f4a3890dbcc9f6f15f6ce

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08217064B2