Sodium Nitrite → Ethyl 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate

HRID 385428Notes

Reaction equation

HRID 385428 reaction equation
N[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[CH:6][C:5]([C:18]2([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:21][CH2:20][CH2:19]2)=[CH:4][C:3]=1[O:27][CH2:28][C:29]([F:32])([F:31])[F:30].N([O-])=O.[Na+].CC#N.O.[ClH:41]>O.Cl[Cu]>[Cl:41][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[CH:6][C:5]([C:18]2([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:21][CH2:20][CH2:19]2)=[CH:4][C:3]=1[O:27][CH2:28][C:29]([F:32])([F:31])[F:30]

Participants

6

Reactant 3

HCID 23668193Sodium NitriteHCID 57995651Ethyl 1-(6-amino-5-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylateHCID 86615699Acetonitrile-hcl-water

Product 1

HCID 57995543Ethyl 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 962WaterSolvent2×

Conditions

Temperature
70 °C

Procedure

Ethyl 1-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate (0.280 g, 0.64 mmol) was dissolved in a mixture of MeCN/H2O/HCl 10 mL/10 mL/4 mL at 0° C. A solution of NaNO2 (0.066 g, 0.96 mmol) in water (2 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 (0.32 g, 3.2 mmol) in water (2 mL) was added drop wise at 0° C. The reaction mixture was heated to 70° C. for 1 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 to give oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate as a yellow oil (0.110 g).

Workup

  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
  7. customto give oil
  8. customThe oil was purified by chromatography over silica gel (hexane/EtOAc)

Sources & evidence

ORD record
ord-6c10340fbbab4bad8b5d32236b74da8e
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

Loading…