Pyrrolidine → 7-pyrrolidin-1-yl-3,4-dihydro-2H-naphthalen-1-one

HRID 2089474Notes

Reaction equation

HRID 2089474 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][C:9]2=[O:12])=[CH:4][CH:3]=1.[NH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>ClCCl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[N:13]1([C:2]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][CH2:8][C:9]3=[O:12])=[CH:4][CH:3]=2)[CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

8

Reactant 4

HCID 31268PyrrolidineHCID 2527317-Bromo-1,2,3,4-tetrahydronaphthalen-1-oneHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxide

Product 1

HCID 591994477-pyrrolidin-1-yl-3,4-dihydro-2H-naphthalen-1-one

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A dry flask is charged with 7-bromo-3,4-dihydro-2H-naphthalen-1-one (CAS#32281-97-3, 0.102 g, 0.454 mmol), pyrrolidine (0.065 g, 0.909 mmol), 2-(di-t-butylphosphino)-biphenyl (0.020 g, 0.067 mmol), sodium tert-butoxide (0.087 g, 0.905 mmol) and toluene (3 mL). The flask is evacuated and filled with nitrogen three times. Pd2(dba)3 (0.041 g, 0.045 mmol) is added and the mixture is heated to reflux for 3 hours, whereupon the mixture is cooled to room temperature, diluted with dichloromethane and washed with water. The organic phase is dried over sodium sulfate and concentrated. The resulting residue is purified by silica gel chromatography (elution with hexanes-ethyl acetate mixtures) to give 7-pyrrolidin-1-yl-3,4-dihydro-2H-naphthalen-1-one; 1H NMR (400 MHz, CDCl3) δ ppm 1.99-2.03 (m, 4 H), 2.06-2.14 (m, 2 H), 2.60-2.65 (m, 2 H), 2.87 (t, J=6.1 Hz, 2 H), 3.28-3.35 (m, 4 H), 6.75 (dd, J=8.3, 2.8 Hz, 1 H), 7.12 (d, J=8.3 Hz, 1 H), 7.19 (d, J=2.8 Hz, 1 H).

Workup

  1. customThe flask is evacuated
  2. additionfilled with nitrogen three times
  3. temperaturethe mixture is heated
  4. temperatureto reflux for 3 hours, whereupon the mixture
  5. washwashed with water
  6. dry with materialThe organic phase is dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe resulting residue is purified by silica gel chromatography (elution with hexanes-ethyl acetate mixtures)

Sources & evidence

ORD record
ord-d7d36c28a99e4eb18bddf3838671b429
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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