Chlorotrimethylsilane → 1,1-Dimethylethyl 3-(2-quinolinyl)-1-azetidinecarboxylate

HRID 1772643Notes

Reaction equation

HRID 1772643 reaction equation
BrCCBr.C[Si](Cl)(C)C.I[CH:11]1[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12]1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.Br[C:39]1[CH:48]=[CH:47][C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[N:40]=1>C1COCC1.[Zn].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]>[N:40]1[C:41]2[C:46](=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH:47]=[CH:48][C:39]=1[CH:11]1[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12]1

Participants

9

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 521585Tris(furan-2-yl)phosphaneHCID 27627562-BromoquinolineHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylate

Product 1

HCID 585484391,1-Dimethylethyl 3-(2-quinolinyl)-1-azetidinecarboxylate

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
65 °C

Procedure

To a stirred suspension of Zn dust (1.70 g, 26.0 mmol) in THF (5 mL) under an Argon atmosphere, 1,2-dibromoethane (250 μl) was added at rt. The resulting mixture was heated at 65° C. for 3 min and allowed to cool to rt. TMSCl (350 μl) was then added and the mixture was stirred at rt for 30 min. tert-Butyl 3-iodoazetidine-1-carboxylate (5.70 g, 20.0 mmol) in THF (15 mL) was then added slowly and the resulting mixture was allowed to stir at rt for 45 min. A solution of Pd2(dba)3 (183 mg, 0.200 mmol) and trifurylphosphine (186 mg, 0.801 mmol) in THF (5 mL) were stirred at rt for 10 min under an Argon atmosphere and the resulting mixture was added to the organozinc reagent prepared, followed by addition of 2-bromoquinoline (5.00 g, 24.0 mmol). The mixture was then heated at 65° C. for 48 h under Argon. The reaction mixture was allowed to cool to rt and filtered through a pad of diatomaceous earth. The filtrate was concentrated and the residue obtained was purified by flash column chromatography on silica gel (0:1-1:0% EtOA/heptanes) to obtain tert-butyl 3-(quinolin-2-yl)azetidine-1-carboxylate.

Workup

  1. temperatureto cool to rt
  2. additionwas then added slowly
  3. customprepared
  4. temperatureThe mixture was then heated at 65° C. for 48 h under Argon
  5. temperatureto cool to rt
  6. filtrationfiltered through a pad of diatomaceous earth
  7. concentrationThe filtrate was concentrated
  8. customthe residue obtained
  9. customwas purified by flash column chromatography on silica gel (0:1-1:0% EtOA/heptanes)

Sources & evidence

ORD record
ord-4e66e30b22dc491fbb673e9f7f85cdcc
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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