Chlorotrimethylsilane → HCID 86644578, compound

HRID 1891229Notes

Reaction equation

HRID 1891229 reaction equation
BrCCBr.C[Si](Cl)(C)C.I[CH:11]1[CH2:14][N:13]([C:15]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])=[O:16])[CH2:12]1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.I[C:39]1[CH:48]=[CH:47][C:42]([C:43]([O:45][CH3:46])=[O:44])=[CH:41][CH:40]=1>C1COCC1.CCOC(C)=O.C([O-])(O)=O.[Na+].[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]>[CH3:46][O:45][C:43]([C:42]1[CH:47]=[CH:48][C:39]([CH:11]2[CH2:14][N:13]([C:15]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])=[O:16])[CH2:12]2)=[CH:40][CH:41]=1)=[O:44]

Participants

11

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 69273Methyl 4-iodobenzoateHCID 521585Tris(furan-2-yl)phosphaneHCID 17791227HCID 17791227, compound

Product 1

HCID 86644578HCID 86644578, compound

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent4×HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
65 °C

Procedure

An oven dried glass vial was charged with zinc powder (120 mg, 1.837 mmol). THF (0.5 mL) was added, followed by 1,2-dibromoethane (15 μL, 0.17 mmol), and the resulting mixture was placed in a pre-heated (65° C.) oil bath. After 10 min, the mixture was allowed to cool to room temperature, TMSCl (18 μL, 0.141 mmol) was added, and the resulting mixture was stirred at room temperature. After 30 min, a solution of tent-butyl 3-iodoazetidine-1-carboxylate (400 mg, 1.41 mmol) in THF (1 mL) was added, and the mixture was stirred at room temperature. After 45 min, a solution of tris(dibenzylideneacetone)dipalladium (65 mg, 0.071 mmol) and tri(2-furyl)phosphine (66 mg, 0.283 mmol) in THF (1 mL) was added, followed by a solution of methyl 4-iodobenzoate (444 mg, 1.70 mmol) in THF (1 mL). The septum and nitrogen inlet were quickly replaced with a teflon cap, and the reaction mixture was heated at 65° C. After 18 h, the mixture was allowed to cool to room temperature, then was diluted with EtOAc and poured in sat aq NaHCO3. The organic phase was separated and concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 25% EtOAc in hexanes, then 25 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 235.9 [M-tBu]+; 1H NMR (500 MHz, CDCl3) δ 8.02 (d, J=8.5 Hz, 2H), 7.39 (d, J=8.5 Hz, 2H), 4.35 (t, J=7.5 Hz, 2H), 3.99-3.95 (m, 2H), 3.92 (s, 3H), 3.81-3.76 (m, 1H), 1.47 (s, 9H).

Workup

  1. customAn oven dried glass vial
  2. temperatureto cool to room temperature
  3. waitAfter 30 min
  4. stirringthe mixture was stirred at room temperature
  5. waitAfter 45 min
  6. customcap
  7. temperaturethe reaction mixture was heated at 65° C
  8. waitAfter 18 h
  9. temperatureto cool to room temperature
  10. customThe organic phase was separated
  11. concentrationconcentrated in vacuo
  12. customPurification by flash chromatography on silica gel (0 to 25% EtOAc in hexanes

Sources & evidence

ORD record
ord-1faacfc16ce047d381a834bc2cb0e315
Source dataset
uspto-grants-2013_08
Patent number
US08507512B2

Reaction notes

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