Sodium Bicarbonate → 4-Phenyl-3-(1-phenylcyclopropyl)-8-(trifluoromethyl)quinoline

HRID 2104599Notes

Reaction equation

HRID 2104599 reaction equation
[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.[C:12]1([C:18]2([CH2:21][CH2:22]O)[CH2:20][CH2:19]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[NH2:24][C:25]1[C:30]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:28]=[CH:27][C:26]=1[C:35]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CC(O)=O>[C:37]1([C:35]2[C:26]3[C:25](=[C:30]([C:31]([F:32])([F:33])[F:34])[CH:29]=[CH:28][CH:27]=3)[N:24]=[CH:22][C:21]=2[C:18]2([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:20][CH2:19]2)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 136403132-(1-Phenylcyclopropyl)ethanolHCID 21555860HCID 21555860, compoundHCID 178418287HCID 178418287, compound

Product 1

HCID 669132914-Phenyl-3-(1-phenylcyclopropyl)-8-(trifluoromethyl)quinolineYield 17%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
120 °C

Procedure

Pyridinium chlorochromate (0.417 g, 1.94 mmol) in CH2Cl2 (3 mL) is treated with a mixture of 2-(1-phenylcyclopropyl)ethanol (0.157 g, 0.967 mmol) in CH2Cl2 (2 mL) for 2 h. The reaction is filtered through Celite, treated with AcOH (3 mL) and [2-amino-3-(trifluoromethyl)phenyl](phenyl)methanone (0.128 g, 0.484 mmol), and the methylene chloride is removed in vacuo. Then 1:20H2SO4:AcOH (0.1 mL) is added and the reaction is heated at 120° C. for 3.5 h. The cooled reaction is poured into saturated aq sodium bicarbonate and extracted with ethyl acetate. The extract is washed with saturated aq sodium bicarbonate and dried (MgSO4). The residue is chromatographed eluting with 5:95 ethyl acetate:hexane and then prep HPLC with a gradient of 10-100% acetonitrile/water to afford the title compound (0.032 g). HRMS: calcd for C25H18F3N+H, 390.14696; found (ESI, [M+H]+), 390.1468.

Workup

  1. filtrationThe reaction is filtered through Celite
  2. customthe methylene chloride is removed in vacuo
  3. additionThen 1:20H2SO4:AcOH (0.1 mL) is added
  4. customThe cooled reaction
  5. extractionextracted with ethyl acetate
  6. washThe extract is washed with saturated aq sodium bicarbonate
  7. dry with materialdried (MgSO4)
  8. customThe residue is chromatographed
  9. washeluting with 5:95 ethyl acetate

Sources & evidence

ORD record
ord-9ebad7db2ce2473fbdd434ca636c7445
Source dataset
uspto-grants-2009_08
Patent number
US07576215B2

Reaction notes

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