1,2-Dichloroethane → HCID 57470079, compound

HRID 1779039Notes

Reaction equation

HRID 1779039 reaction equation
ClCCCl.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.I[C:39]1[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[CH:41][CH: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+:45]([C:42]1[CH:43]=[CH:44][C:39]([CH:11]2[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12]2)=[CH:40][CH:41]=1)([O-:47])=[O:46]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 6397ChlorotrimethylsilaneHCID 124951-Iodo-4-nitrobenzeneHCID 521585Tris(furan-2-yl)phosphaneHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylate

Product 1

HCID 57470079HCID 57470079, compound

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
80 °C

Procedure

DCE (0.146 mL, 1.69 mmol) was added to a vigorously stirred suspension of zinc dust (0.901 g, 13.8 mmol) in THF (3.5 mL) under nitrogen. The resulting suspension was heated at 80° C. for 10 minutes then cooled to room temperature. Trimethylsilyl chloride (0.202 mL, 1.59 mmol) in THF (1.75 mL) was added and the mixture was stirred at room temperature for 4 minutes. A solution of tert-butyl 3-iodoazetidine-1-carboxylate (3.00 g, 10.6 mmol) in THF (3.5 mL) was added dropwise over 15 minutes and the resulting mixture stirred at room temperature for 2 hours. Pd2(dba)3 (0.155 g, 0.170 mmol) and tri-2-furylphosphine (0.143 g, 0.615 mmol) were added followed by 1-iodo-4-nitrobenzene (2.90 g, 11.7 mmol) in THF (18 mL). The resulting mixture was then heated at 55° C. for 3 hours then quenched with an aqueous saturated sodium chloride solution (15 mL). After filtration through a pad of Celite, the layers were separated and the aqueous phase extracted with DCM (2×15 mL). The combined organic fractions were dried (MgSO4), filtered and evaporated in vacuo. The residue was purified using silica gel column chromatography (CombiFlash Rf, 40 g SiO2 cartridge, 10-40% EtOAc in cyclohexane) to give the title compound A76 as an orange oil (2.14 g, 72%); 1H NMR (300 MHz, CDCl3) δ 8.24 (dd, J=6.8, 1.9 Hz, 2H), 7.51 (d, J=8.6 Hz, 2H), 4.41 (t, J=8.7 Hz, 2H), 3.98 (dd, J=8.5, 5.7 Hz, 2H), 3.89-3.81 (s, 1H), 1.49 (s, 9H).

Workup

  1. temperaturethen cooled to room temperature
  2. stirringthe resulting mixture stirred at room temperature for 2 hours
  3. temperatureThe resulting mixture was then heated at 55° C. for 3 hours
  4. customthen quenched with an aqueous saturated sodium chloride solution (15 mL)
  5. filtrationAfter filtration through a pad of Celite
  6. customthe layers were separated
  7. extractionthe aqueous phase extracted with DCM (2×15 mL)
  8. dry with materialThe combined organic fractions were dried (MgSO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe residue was purified

Sources & evidence

ORD record
ord-c3cf90d91f594c2fb266307694653594
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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