Tris(1,1-dimethylethyl)phosphine → HCID 59807131, compound

HRID 1922399Notes

Reaction equation

HRID 1922399 reaction equation
P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.Br[C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]([CH:25]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26]1)[CH2:20][CH2:19][CH2:18]2.[F-].C([N+:42](CCCC)(CCCC)CCCC)CCC>C1COCC1.CO.C(Cl)Cl.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]>[NH2:42][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]([CH:25]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26]1)[CH2:20][CH2:19][CH2:18]2

Participants

7

Reactant 3

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2724141Tetrabutylammonium FluorideHCID 53392445HCID 53392445, compound

Product 1

HCID 59807131HCID 59807131, compoundYield 93.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent3×HCID 21226129Dichloromethane methanolSolvent

Procedure

A suspension of Pd2(dba)3 (46 mg, 0.05 mmol) in 2 mL anhydrous THF was treated with PtBu3 (600 μL of a 10% wt in hexanes solution, 0.2 mmol) and stirred at room temperature for 5 minutes. A solution of tert-butyl 3-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)pyrrolidine-1-carboxylate (381 mg, 1.00 mmol) followed by lithium hexamethyldisilizane (2.0 mL of a 1 M solution in THF, 2.0 mmol). The resulting dark brown suspension was heated at 95° C. for 1.5 hours. The mixture was cooled to room temperature and treated with 8 ml of a 1M tetrabutylammonium fluoride solution in THF then stirred at room temperature for 20 minutes. The mixture was partitioned between Et2O (100 mL) and H2O (20 mL). After extraction, the organic layer was separated and the aqueous layer was extracted once more with Et2O (50 mL). The combined organic fractions were dried over Na2SO4, filtered and concentrated to give a dark brown residue. This residue was subjected to flash chromatography on silica gel using 2.5% 2M NH3 in MeOH/CH2Cl2 to give a viscous dark brown residue (295 mg, 93.1%). 1H-NMR (CDCl3) δ 6.59-6.44 (m, 3H), 4.35-4.23 (m, 1H), 3.59-3.11 (m, 8H), 2.69 (t, J=6.3 Hz, 2H), 2.09-2.04 (m, 2H), 1.93-1.87 (m, 2H), 1.47 (s, 9H). MS (ESI): 318.2 (M+1, 100%).

Workup

  1. temperatureThe resulting dark brown suspension was heated at 95° C. for 1.5 hours
  2. temperatureThe mixture was cooled to room temperature
  3. stirringthen stirred at room temperature for 20 minutes
  4. customThe mixture was partitioned between Et2O (100 mL) and H2O (20 mL)
  5. extractionAfter extraction
  6. customthe organic layer was separated
  7. extractionthe aqueous layer was extracted once more with Et2O (50 mL)
  8. dry with materialThe combined organic fractions were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a dark brown residue

Sources & evidence

ORD record
ord-a39bf77c5cb146f7af0fbb417be72f88
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

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