Chlorotrimethylsilane → HCID 57470079, compound

HRID 592343Notes

Reaction equation

HRID 592343 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.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]>[C:18]([O:17][C:15]([N:13]1[CH2:14][CH:11]([C:39]2[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[CH:41][CH:40]=2)[CH2:12]1)=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

9

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 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

1,2-Dibromoethane (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 a nitrogen atmosphere and the resulting suspension heated at 80° C. for 10 minutes. Trimethylsilyl chloride (0.202 mL, 1.59 mmol) in THF (1.75 mL) was added at room temperature and after stirring 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 a period of 15 minutes. The resulting mixture was stirred at room temperature for 2 hours then 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 heated at 55° C. for 3 hours then quenched at room temperature with a saturated aqueous sodium chloride solution (15 mL). The aqueous phase was extracted with DCM (2×15 mL) then the combined organic fractions were dried (magnesium sulfate), 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 I6 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. additionwas added dropwise over a period of 15 minutes
  2. temperatureThe resulting mixture was heated at 55° C. for 3 hours
  3. customthen quenched at room temperature with a saturated aqueous sodium chloride solution (15 mL)
  4. extractionThe aqueous phase was extracted with DCM (2×15 mL)
  5. dry with materialthe combined organic fractions were dried (magnesium sulfate)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified

Sources & evidence

ORD record
ord-b05bafa2270640189f558c9363337560
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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