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

HRID 1512466Notes

Reaction equation

HRID 1512466 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][CH:29]1[CH2:31][CH2:30]1.N([O-])=O.[Na+].CC#N.O.[ClH:40]>O.Cl[Cu]>[Cl:40][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][CH:29]1[CH2:31][CH2:30]1

Participants

6

Reactant 3

HCID 23668193Sodium NitriteHCID 57995480Ethyl 1-(6-amino-5-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylateHCID 86615699Acetonitrile-hcl-water

Product 1

HCID 57995490Ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 962WaterSolvent2×

Conditions

Temperature
70 °C

Procedure

Ethyl 1-(6-amino-5-(cyclopropylmethoxy)-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 under reduced pressure. 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 crude black oil which was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate (0.10 g) as yellow oil.

Workup

  1. customthe solvent was evaporated under reduced pressure
  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 crude black oil which
  8. customwas purified by chromatography over silica gel (hexane/EtOAc)

Sources & evidence

ORD record
ord-ca218d805e834b5a8914d48a292224d7
Source dataset
uspto-grants-2012_07
Patent number
US08217064B2

Reaction notes

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