Tetrahydrofuran → 1-(4-Tert-butylphenyl)-2,5-bis(4-((trimethylsilyl)ethynyl)phenyl)pyrrolidine

HRID 1470979Notes

Reaction equation

HRID 1470979 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH:10]([C:13]3[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=3)[N:9]2[C:20]2[CH:25]=[CH:24][C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:22][CH:21]=2)=[CH:4][CH:3]=1.[CH2:30]1[CH2:34]OCC1.[CH3:35][Si:36]([C:39]#[CH:40])([CH3:38])[CH3:37].[Al]>CCOCC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C(N(CC)CC)C>[C:26]([C:23]1[CH:22]=[CH:21][C:20]([N:9]2[CH:10]([C:13]3[CH:18]=[CH:17][C:16]([C:40]#[C:39][Si:36]([CH3:38])([CH3:37])[CH3:35])=[CH:15][CH:14]=3)[CH2:11][CH2:12][CH:8]2[C:5]2[CH:6]=[CH:7][C:2]([C:34]#[C:30][Si:36]([CH3:38])([CH3:37])[CH3:35])=[CH:3][CH:4]=2)=[CH:25][CH:24]=1)([CH3:29])([CH3:28])[CH3:27]

Participants

9

Reactant 4

HCID 8028TetrahydrofuranHCID 66111Trimethylsilylacetylene2×HCID 5359268AluminumHCID 582268372,5-Bis(4-bromophenyl)-1-(4-tert-butylphenyl)pyrrolidine

Product 1

HCID 687942901-(4-Tert-butylphenyl)-2,5-bis(4-((trimethylsilyl)ethynyl)phenyl)pyrrolidineYield 89%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418476HCID 178418476, compoundCatalyst2×HCID 3283Diethyl EtherSolventHCID 8471TriethylamineSolvent

Procedure

To an oven-dried microwave tube (Size M, 5 mL) purged with nitrogen, added the product of Example 42C (340 mg, 0.662 mmol), bis(triphenylphosphine)palladium(II) dichloride (18.60 mg, 0.026 mmol), THF (2 mL), and triethylamine (2 mL). Stirred at room temperature for 5 min, then added copper(I) iodide (2.52 mg, 0.013 mmol), stirred the yellow mixture for 2 min, then nitrogen bubbled through for 15 min. Added trimethylsilylacetylene (0.374 mL, 2.65 mmol), sealed the tube with an aluminum crimp cap, and heated in an oil bath at 70° C. for 20 hr. Cooled the reaction to room temperature, added fresh bis(triphenylphosphine)palladium(II) dichloride (18.60 mg, 0.026 mmol) and copper(I) iodide (2.52 mg, 0.013 mmol), added additional trimethylsilylacetylene (0.374 mL, 2.65 mmol), and continued heating at 80° C. for 24 hr. Cooled the reaction to room temperature, diluted with Et2O (50 mL), washed with H2O (2×25 mL) and brine (25 mL), dried the organic phase over anhydrous MgSO4, filtered, and concentrated by rotary evaporation to a light tan foam (470 mg). Purified by flash chromatography (silica gel, 2.5 cm×10 cm, 2% Et2O/hexanes) to afford the title product as a yellow foam (324 mg, 89%) as a mixture of stereoisomers. MS (ESI+) m/z 548 (M+H)+.

Workup

  1. customTo an oven-dried microwave tube (Size M, 5 mL) purged with nitrogen
  2. customnitrogen bubbled through for 15 min
  3. temperatureheated in an oil bath at 70° C. for 20 hr
  4. temperatureCooled
  5. customthe reaction to room temperature
  6. temperaturecontinued heating at 80° C. for 24 hr
  7. temperatureCooled
  8. customthe reaction to room temperature
  9. washwashed with H2O (2×25 mL) and brine (25 mL)
  10. dry with materialdried the organic phase over anhydrous MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated by rotary evaporation to a light tan foam (470 mg)
  13. customPurified by flash chromatography (silica gel, 2.5 cm×10 cm, 2% Et2O/hexanes)

Sources & evidence

ORD record
ord-540458d8a3ae40d0b0403880f1d84ada
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

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