Water → 5-(5-Phenyl-1-pentynyl)-3-(1-methyl-2-(s)-pyrrolidinylmethoxy)pyridine

HRID 2305094Notes

Reaction equation

HRID 2305094 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[CH3:15])[CH:5]=[N:6][CH:7]=1.[C:16]1([CH2:22][CH2:23][CH2:24][C:25]#[CH:26])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CCN(CC)CC.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:16]1([CH2:22][CH2:23][CH2:24][C:25]#[C:26][C:2]2[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]3[CH2:14][CH2:13][CH2:12][N:11]3[CH3:15])[CH:5]=[N:6][CH:7]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

9

Reactant 4

HCID 962WaterHCID 745735-Phenyl-1-pentyneHCID 516892Sodium BicarbonateHCID 11288721HCID 11288721, compound

Product 1

HCID 542589465-(5-Phenyl-1-pentynyl)-3-(1-methyl-2-(s)-pyrrolidinylmethoxy)pyridineYield 81.9%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 5-bromo-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)-pyridine (408 mg, 1.50 mmol), bis(triphenylphosphine)palladium(II) chloride (21 mg, 0.029 mmol) and copper (I) iodide (5 mg, 0.029 mmol) in CH2Cl2 (3.0 mL) and NEt3 (1.0 mL) was added 5-phenyl-1-pentyne (324 mg, 2.25 mmol). The mixture was refluxed overnight then cooled to room temperature. Water (2 mL) was added, and solid sodium bicarbonate was added until the aqueous layer was saturated. The mixture was extracted with EtOAc, which was dried over MgSO4, filtered and concentrated. The residue was chromatographed on a silica gel column, eluting with NH4OH/MeOH/EtOAc 0:1:9 and 1:10:90 to afford an oil (411 mg, 80%). MS (CI/NH3) m/z 335 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.65-2.10 (m, 6H), 2.26-2.37 (m, 1H), 2.41-2.47 (m, 2H), 2.48 (s, 3H), 2.61-2.73 (m, 1H), 2.76-2.83 (m, 2H), 3.07-3.16 (m, 1H), 3.89-4.03 (m, 2H), 7.17-7.36 (m, 6H), 8.21-8.26 (m, 2H).

Workup

  1. temperatureThe mixture was refluxed overnight
  2. extractionThe mixture was extracted with EtOAc, which
  3. dry with materialwas dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a silica gel column
  7. washeluting with NH4OH/MeOH/EtOAc 0:1:9 and 1:10:90

Sources & evidence

ORD record
ord-8970a075766e4ab9a3230006a8ac3fde
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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