Diisopropylamine → (2R)-1-[2-(5-bromo-1-benzofuran-2-yl)ethyl]-2-methylpyrrolidine

HRID 494858Notes

Reaction equation

HRID 494858 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4](I)[CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(NC(C)C)(C)C.[CH2:36]([N:40]1[CH2:44][CH2:43][CH2:42][C@H:41]1[CH3:45])[CH2:37][C:38]#[CH:39]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Cu]I.CC#N>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[O:8][C:38]([CH2:37][CH2:36][N:40]3[CH2:44][CH2:43][CH2:42][C@H:41]3[CH3:45])=[CH:39][C:4]=2[CH:3]=1

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 11776TriphenylphosphineHCID 109245324-Bromo-2-iodophenolHCID 11367023(R)-1-(But-3-yn-1-yl)-2-methylpyrrolidine

Product 1

HCID 11220543(2R)-1-[2-(5-bromo-1-benzofuran-2-yl)ethyl]-2-methylpyrrolidineYield 26%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Procedure

4-Bromo-2-iodophenol (2.99 g, 90% pure, 9 mmol), palladium (II) acetate (112 mg, 0.50 mmol), triphenylphosphine (262 mg, 1.0 mmol), copper(I) iodide (571 mg, 3.0 mmol), and diisopropylamine (14 mL, 100 mmol) were dissolved into a 0.09 M MeCN solution of (R)-1-but-3-ynyl-2-methylpyrrolidine (120 mL, 10.8 mmol) and stirred at room temperature three days, then at 80° C. overnight. The reaction mixture was cooled to room temperature, concentrated, and chromatographed through a short column of silica with 2:1 hexanes/CH2Cl2 followed by a 0 to 1% gradient of MeOH/CH2Cl2. The appropriate fractions were concentrated, and the residue extracted with MeOH. The extracts were concentrated and partitioned between CH2Cl2 and 1 M aqueous Na2CO3, worked up as usual, dried (Na2SO4), and concentrated to provide the title compound as a dark red syrup (26% yield).

Workup

  1. customat 80° C.
  2. customovernight
  3. temperatureThe reaction mixture was cooled to room temperature
  4. concentrationconcentrated
  5. customchromatographed through a short column of silica with 2:1 hexanes/CH2Cl2
  6. concentrationThe appropriate fractions were concentrated
  7. extractionthe residue extracted with MeOH
  8. concentrationThe extracts were concentrated
  9. custompartitioned between CH2Cl2 and 1 M aqueous Na2CO3
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-5170f195df774e289ab8879b0ebc3300
Source dataset
uspto-grants-2009_05
Patent number
US07538138B2

Reaction notes

Loading…