Tetrahydrofuran → 2-(3-Cyclohexyl-5-fluoro-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester

HRID 1801037Notes

Reaction equation

HRID 1801037 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]([C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[C:18](Br)[CH:17]=1)[C:10]([CH3:25])([CH3:24])[CH2:9]2)=[O:5])[CH3:2].[Br-].[CH:27]1([Zn+])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1.O1CCCC1.[Cl-].[NH4+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]([C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)[CH:17]=1)[C:10]([CH3:25])([CH3:24])[CH2:9]2)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 674437712-(3-Bromo-5-fluoro-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl esterHCID 178418970HCID 178418970, compound

Product 1

HCID 674417422-(3-Cyclohexyl-5-fluoro-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl esterYield 51%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-(3-bromo-5-fluoro-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (0.41 g, 1.0 mmol), cyclohexylzinc bromide solution 0.5 M in tetrahydrofuran (3.0 mL, 1.5 mmol), 1,1′-bis(diphenylphosphino) ferrocenedichloropalladium (II) (41 mg, 0.05 mmol), and DMF (0.5 mL) in dioxane (3 mL) was stirred at 70° C. for 2 hours. Then treated with saturated ammonium chloride (20 mL), extracted with ether (100 mL). After removal of solvent, the residue was purified on flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company) (10% ethyl acetate/hexanes) to afford 2-(3-cyclohexyl-5-fluoro-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (0.21 g, 51%) as a white solid: LC/MS m/e calcd for C26H32FNO2 M+: 410.6, observed: 410.1.

Workup

  1. extractionextracted with ether (100 mL)
  2. customAfter removal of solvent
  3. customthe residue was purified on flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company) (10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-fcf39b71fe7f429ea05cfabc53d5e79a
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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