Chlorotrimethylsilane → Tert-butyl 3-(4-bromo-2-methylphenyl)azetidine-1-carboxylate

HRID 340633

Reaction equation

HRID 340633 reaction equation
BrCCBr.Cl[Si](C)(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:38][C:39]1[CH:40]=[CH:41][C:42](I)=[C:43]([CH3:45])[CH:44]=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].O>[Br:38][C:39]1[CH:40]=[CH:41][C:42]([CH:11]2[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12]2)=[C:43]([CH3:45])[CH:44]=1

Participants

10

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 521585Tris(furan-2-yl)phosphaneHCID 27246015-Bromo-2-iodotolueneHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylate

Product 1

HCID 86692010Tert-butyl 3-(4-bromo-2-methylphenyl)azetidine-1-carboxylate

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
65 °C

Procedure

To a vial with zinc dust (2.77 g, 42.4 mmol) in anhydrous THF (15 mL) under nitrogen was added 1,2-dibromoethane (0.24 mL, 2.83 mmol), then the suspension was stirred at 65° C. for 3 min. After cooling to ambient temperature, chloro(trimethyl)silane (0.36 mL, 2.83 mmol) was added and the mixture was stirred at room temperature for 30 min. Then, a solution of tert-butyl 3-iodoazetidine-1-carboxylate (8.00 g, 28.3 mmol) in THF (10 mL) was added and the mixture was stirred for 45 min. P(2-furyl)3 (1.31 g, 5.7 mmol) and tris(dibenzylidene acetone)dipalladium (0) (2.59 g, 2.83 mmol) were added to a separate vial, dissolved in THF (5 mL) and stirred under nitrogen at ambient temperature for 10 min, then the mixture and 5-bromo-2-iodotoluene (4.84 mL, 33.9 mmol) in THF (10 mL) were added to the organozine reagent solution. The mixture was then placed in a 65° C. oil bath for 2 h. The reaction mixture was allowed to cool to room temperature and then was poured into water. The mixture was extracted with EtOAc, and the organic layer was concentrated in vacuo. Purification by chromatography on silica gel (0 to 50% EtOAc in hexanes, then 50 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 271.8 [M-t-Bu+2H]+; 1H NMR (500 MHz, acetone-d6) δ 7.40-7.30 (m, 3 H),4.23 (br, 2 H),3.99 (m, 1 H),3.91 (m, 2 H),2.21 (s, 3 H),1.42 (s, 9 H).

Workup

  1. temperatureAfter cooling to ambient temperature
  2. stirringthe mixture was stirred at room temperature for 30 min
  3. stirringthe mixture was stirred for 45 min
  4. stirringstirred under nitrogen at ambient temperature for 10 min
  5. customwas then placed in a 65° C.
  6. customfor 2 h
  7. temperatureto cool to room temperature
  8. extractionThe mixture was extracted with EtOAc
  9. concentrationthe organic layer was concentrated in vacuo
  10. customPurification by chromatography on silica gel (0 to 50% EtOAc in hexanes

Sources & evidence

ORD record
ord-c614c8a216174400b1946f5985c42b9c
Source dataset
uspto-grants-2014_11
Patent number
US08895583B2

Linked notes

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