Water → 3-Hex-1-ynyl-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine

HRID 1780298Notes

Reaction equation

HRID 1780298 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.[CH:16]#[C:17][CH2:18][CH2:19][CH2:20][CH3:21].O.C(=O)(O)[O-].[Na+]>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]([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:17][CH2:18][CH2:19][CH2:20][CH3:21]

Participants

8

Reactant 4

HCID 962WaterHCID 127321-HexyneHCID 516892Sodium BicarbonateHCID 112887213-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine

Product 1

HCID 112195103-Hex-1-ynyl-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridineYield 64%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of 5-bromo-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)-pyridine (272 mg, 1.00 mmol), bis(triphenylphosphine)palladium(II) chloride (18 mg, 0.025 mmol) and copper (I) iodide (2 mg, 0.025 mmol) in NEt3 (6.0 mL) was added 1-hexyne (0.237 mL, 2.00 mmol). The mixture was refluxed overnight and 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 (174 mg, 64%). MS (CI/NH3) m/z 273 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ0.96 (t, J=7.0 Hz, 3H), 1.42-2.10 (m, 8H), 2.26-2.37 (m, 1H), 2.43 (t, J=7.0 Hz, 2H), 2.48 (s, 3H), 2.63-2.71 (m, 1H), 3.08-3.16 (m, 1H), 3.88-4.03 (m, 2H), 4.47-4.55 (m, 1H), 7.17-7.21 (m, 1H), 8.19-8.23 (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-ea2c4bdcc973462e9b21939fd5bff85a
Source dataset
uspto-grants-1997_05
Patent number
US05629325

Reaction notes

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