Nitrogen → tert-Butyl 1-benzyl-6-(4-fluorophenyl)-1,2,3,4-tetrahydroquinolin-3-ylcarbamate

HRID 2234253Notes

Reaction equation

HRID 2234253 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][CH:8]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14](Br)[CH:15]=2)[N:10]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[F:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C([O-])([O-])=O.[K+].[K+].N#N>CO.C1COCC1>[CH2:19]([N:10]1[C:11]2[C:16](=[CH:15][C:14]([C:31]3[CH:32]=[CH:33][C:28]([F:27])=[CH:29][CH:30]=3)=[CH:13][CH:12]=2)[CH2:17][CH:8]([NH:7][C:6](=[O:26])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:9]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 59297053(1-Benzyl-6-bromo-1,2,3,4-tetrahydroquinolin-3-yl)-carbamic acid tert-butyl ester

Product 1

HCID 59297041tert-Butyl 1-benzyl-6-(4-fluorophenyl)-1,2,3,4-tetrahydroquinolin-3-ylcarbamateYield 54%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

(1-Benzyl-6-bromo-1,2,3,4-tetrahydroquinolin-3-yl)-carbamic acid tert-butyl ester (2.00 g, 4.79 mmol), prepared as described in Example 29A, 4-fluorophenyl-boronic acid (2.01 g, 14.37 mmol) and K2CO3 (2.65 g, 19.16 mmol) in a mixed solvent of THF (50 mL) and MeOH (25 mL) were stirred at RT for 30 min while N2 was allowed to bubble through the mixture, and then PXPd (258 mg, 0.48 mmol) was added. The reaction mixture was heated at 60° C. under N2 for 3 h. After cooling to RT, the solvent was stripped and the residue was diluted with H2O (60 mL) and CH2Cl2 (100 mL). The aqueous layer was extracted with CH2Cl2 (100 mL×3), and the combined organic extracts were washed with saturated aqueous NaCl (50 mL), dried (Na2SO4), filtered and concentrated. The resulting residue was chromatographed (silica gel) eluting with EtOAc (0-20%) in hexanes to give the title compound (1.11 g, 54%) as a white foam.

Workup

  1. customto bubble through the mixture
  2. additionPXPd (258 mg, 0.48 mmol) was added
  3. temperatureAfter cooling to RT
  4. additionthe residue was diluted with H2O (60 mL) and CH2Cl2 (100 mL)
  5. extractionThe aqueous layer was extracted with CH2Cl2 (100 mL×3)
  6. washthe combined organic extracts were washed with saturated aqueous NaCl (50 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was chromatographed (silica gel)
  11. washeluting with EtOAc (0-20%) in hexanes

Sources & evidence

ORD record
ord-7914193fa2b54362a959efcb494e1c38
Source dataset
uspto-grants-2010_05
Patent number
US07709647B2

Reaction notes

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